Molecular and ecological determinants of viral emergence in tropical regions: a One Health perspective integrating host–pathogen interactions, immune dysregulation, translational diagnostics, and epidemiological surveillance

1 Introduction

Emerging viral diseases are an ongoing threat to public health worldwide amid increased human and animal contact, environmental changes, and the rapid evolution of pathogenic viruses. In the past fifty years, there have been more than 40 infectious diseases, about 75% of which have zoonotic origins (1). RNA viruses are responsible for a considerable part of these pathogen infections due to their mutation speed, genetic recombination, and evolutionary plasticity, which allow them to invade different organisms and niches (2). Instead of interpreting each case of emerging viruses as being a result of a certain event at an ecological or molecular level, current research suggests that viral emergence is a consequence of a combination of various environmental, biological, and socioeconomical factors that operate at different spatial and temporal levels.

Viral emergence is significantly influenced by tropical regions, as they possess great biodiversity, numerous wildlife hosts, and favorable weather conditions for arthropod carriers as well as changing landscapes shaped by humans (3, 4). Such environments present a perfect setting for interaction between wildlife, domestic animals, vectors, and humans and provide conditions for both spillover (when a virus from animals infects humans) and spillback (the reverse process) of viruses, which are now considered to be essential parts of the One Health concept. This means that studying viral emergence in tropical ecosystems should involve checking ecological, molecular, immunological, and epidemiological procedures rather than just separate aspects of risk factors.

The expansion of ecological disruption has heightened the possibility of transmitting pathogens. Deforestation, agricultural expansion, forest fragmentation, urbanization, mining activities, and other land-use changes continue changing natural habitats and connecting animals and humans (5). Climate change alters some processes by having an impact on temperature, rainfall, and seasonality, which influences pathogen persistence, vector numbers, and geographical distribution (6). It is worth mentioning that although tropical regions remain a significant hotspot for infectious disease emergence, the climate-induced spread of vectors and animal carriers shows the emergence of risks even in subtropical and temperate areas (7). For this reason, the emergence of the virus should be assessed as an ecological process influenced by both local and global environmental changes.

Host diversity is a crucial component of the emergence of viral pathogens, but its function is quite complex. For instance, tropical regions are noted for their high variety of mammals, such as bats, rodents, and monkeys, which act as reservoirs of various viruses through coevolution with host–pathogen systems (8). Nevertheless, the connection between host diversity and the occurrence of infections has not reached an agreement among scientists yet. Some studies suggest that having more biodiversity results in fewer chances for transmission because the chances of meeting an adequate host and of transmitting a virus decrease (9). On the contrary, there are studies pointing out that having many hosts and vectors due to disturbance might lead to an increase in the chances of virus transmission (10).

Emergence of viruses at the molecular level involves evolutionary processes that allow pathogens to break through the barriers between species. RNA viruses undergo mutations at rates much higher than that of vertebrates, thus producing genetically diverse quasispecies that can quickly adapt to environmental and immunological conditions (11). Successful transmission from one species to another requires several molecular changes, including improvement in receptor binding, increased replication efficiency, and development of mechanisms that can prevent or reduce innate immune reactions of the host (12). Hence, the evolutionary processes work together with environmental ones to ensure the emergence of viruses.

Finally, the innate immune response is vital in controlling initial viral replication and enabling the eradication of the pathogens. However, successful viral emergence often relies on the processes that help to escape or down-regulate the immune responses of the host, instead of simply overpowering them. Innate immune pathways, such as interferon-related antiviral responses, are essential in the battle against viral invasion. In addition to that, many tropical viruses have invented methods to prevent the synthesis of interferons and their action (13). The occurrence of excessive and uncontrolled immune activation and responses is connected with the pathogenesis of many emerging viral diseases, including dengue fever, chikungunya fever, Ebola virus disease, and henipavirus infections (14).

In addition to the immune responses that are innate or genetic, there is also an impact of adaptive immunity on the emergence of viruses, as well as on the severity and the outcome of disease. There are factors such as immune memory, T-cell activity that is cross-reactive, and the possibility of antibodies to provide cross-protection that might help in decreasing the effects of infection caused by a close virus, but sometimes having a previous immunity may lead to an immunopathological phenomenon known as antibody-dependent enhancement (ADE).

In spite of significant progress achieved in ecological monitoring, molecular virology, and immunology, studies conducted so far have analyzed these factors more or less independently. Very few articles combine ecological changes, viruses’ evolution, and immune reactions by the host in a consistent framework of “One Health.” Additionally, conceptual models previously used did not always take into account the impact of spillover–spillback dynamics and the interaction among ecological, molecular, and immunological factors influencing the emergence of viruses (15).

The purpose of this review is to summarize what we know at this moment regarding the factors that determine the emergence of viruses in tropical regions with respect to four main tasks:

• List the ecological factors affecting the emergence of viruses, such as climate change, land changes and forest fragmentation, urbanization, vector ecology, and the dynamics with the reservoir host;
• Discuss molecular properties that permit the adaptation of viruses, such as receptor evolution, genetic diversity of viruses, mechanisms of evasion from host immunity, and interspecies transmission;
• Study host-pathogen interactions focusing on both types of immune responses and on issues such as immune impairment, immune recall, and cross-reaction immunity; and
• Discuss recent achievements in such fields as translational medicine, molecular epidemiology, genomic tracking, and recently introduced point-of-care methods that improve the capabilities of virus detection in tropical areas.

This review synthesizes multidisciplinary knowledge within the One Health framework. By doing this, the review will allow us to see what we know and what we do not know about the issue discussed. Furthermore, the review will point out the most significant areas for future research and thus provide a necessary theoretical framework for further studies regarding how to deal with the threats posed by new viral diseases in tropical habitats.

Thus, the authors of the review offer the creation of a new conceptual map, i.e., the Tropical Viral Emergence Risk Index (TVERI), which would help to undertake different types of assessment of the risks of viral emergence based on the data related to its ecology, molecular biology, and immunology. However, people should remember that TVERI is not a meaningful risk assessment formula, but rather a system of concepts. Further improvement and theoretical development will be essential for its practical use. The integrated conceptual framework is illustrated in Figure 1.

2 Methods

This study was designed as a structured narrative review to synthesize and critically evaluate current evidence on the ecological, molecular, immunological, and translational determinants of viral emergence in tropical and subtropical regions. A structured narrative approach was selected because the objective was to integrate multidisciplinary evidence, identify knowledge gaps, and propose a conceptual framework (TVERI), rather than to perform a quantitative meta-analysis or a formal systematic review.

2.1 Review design

This study was conducted as a structured narrative review to synthesize and critically evaluate the current evidence on the ecological, molecular, immunological, and translational determinants of viral emergence in tropical and subtropical regions. A structured narrative review was considered the most appropriate approach because the objective was to integrate multidisciplinary evidence, identify current knowledge gaps, and propose a conceptual framework, the Tropical Viral Emergence Risk Index (TVERI), rather than to perform a formal systematic review, meta-analysis, or quantitative evidence synthesis. To improve methodological transparency, the literature search and study selection procedures are described in detail below.

2.2 Literature search methodology

A detailed literature search was undertaken with the aim of identifying peer-reviewed publications regarding issues of viral emergence primarily in the tropical and subtropical territory. The search concentrated on papers published within the time frame between October 1st, 2000, and December 31st, 2025, in four famous electronic databases: PubMed, Web of Science, Scopus, and Google Scholar.

The searching technique included employing different combinations of search words in coordination with Boolean operators (AND/OR). The search words included “viral emergence,” “tropical zoonotic viruses,” “spillover,” “spillback,” “host-pathogen interaction,” “immune dysregulation,” “One Health,” “RNA virus evolution,” “molecular diagnostics,” “viral surveillance,” and other related terms. Eventually, the reference lists of the recent review articles and research papers were screened manually in order to find the additional eligible publications.

2.3 Study selection and eligibility

Eligible publications were selected according to predefined inclusion and exclusion criteria.

Inclusion Criteria

• Peer-reviewed original research articles, systematic reviews, narrative reviews, and meta-analyses.
• Studies investigating ecological, molecular, immunological, epidemiological, diagnostic, or One Health aspects of viral emergence in tropical or subtropical regions.
• Publications written in English.
• Studies considered scientifically relevant to the objectives of this review.

Exclusion Criteria

• Conference abstracts, editorials, opinion articles, correspondence, and non-peer-reviewed publications.
• Studies conducted solely in environments that lack tropical relevance in the context of viral emergence.
• Studies that exclusively deal with bacterial, fungal, or parasitic diseases with no viral component.
• Duplicated publications and studies without adequate methodological or scientific content.

Titles and summaries were skimmed at the onset to determine relevance first, after which the full text of the candidate articles was scrutinized. Additional publications identified through citation tracking of key articles were included when they met the eligibility criteria. The selection of studies took place in two consecutive steps. First, the titles and abstracts were evaluated for relevance, and the full texts of articles deemed potentially eligible were reviewed in accordance with the previously determined criteria for eligibility. Before a final screening, duplicate records found among the databases were eliminated. The literature search identified 1,300 records across four databases. After removing duplicates (n = 350), 950 records were screened by title and abstract. Of these, 770 records were excluded as clearly irrelevant, and 180 full-text articles were assessed for eligibility. During full-text review, 93 articles were excluded, primarily due to non-tropical focus (n = 35), non-viral pathogens (n = 25), or non-peer-reviewed formats (n = 15). An additional 38 articles were identified through citation tracking. A total of 115 studies were included in the final narrative synthesis, matching the number of references cited in the manuscript. The study selection process is summarized in (Figure 2).

2.4 Data extraction

Information from eligible studies was extracted qualitatively and organized according to the objectives of the review. Extracted information included the study focus, viral pathogen, host or reservoir species, ecological and environmental drivers, mechanisms of host–pathogen interaction, immune response characteristics, molecular evolution, diagnostic approaches, surveillance strategies, and principal findings related to viral emergence.

Rather than performing a quantitative comparison, emphasis was placed on identifying recurring themes, emerging concepts, areas of consensus, and knowledge gaps across the published literature. It was also crucial to pay attention to the findings of the research that contradict each other, to compare areas of agreement, weaknesses in methodology, and the issues that still require investigation.

2.5 Data synthesis

The extracted evidence was synthesized narratively into four interrelated thematic domains:

• Ecological determinants of viral emergence
• Molecular mechanisms of viral adaptation and evolution
• Host-pathogen interaction and immune dysregulation
• Translational applications, including diagnostics, surveillance, and One Health strategies.

Although this review was conducted as a structured narrative review rather than a formal systematic review, quantitative risk-of-bias assessment or methodological quality scoring was not performed. Nevertheless, the methodological rigor and scientific relevance of each publication were considered during study selection. These qualitative assessments also informed the narrative synthesis of evidence presented in this review.

These thematic domains were integrated to develop the Tropical Viral Emergence Risk Index (TVERI). The TVERI presented in this review should be interpreted as a conceptual framework intended to facilitate hypothesis generation and multidisciplinary discussion regarding factors influencing viral emergence in tropical ecosystems. The framework is not presented as a validated predictive model and therefore requires future theoretical refinement, empirical testing, sensitivity analysis, and validation using independent epidemiological datasets before routine application.

2.6 Limitations of the review

This review has a few limitations. First of all, it only considered publications in English, which might have led to the omission of studies written in other languages. Secondly, although it carries out a structured narrative review, the study does not involve the formal assessment of the risk of bias or meta-analysis. Thirdly, despite the use of a comprehensive search strategy, there has been a potential effect of publication bias or focused availability of evidence. Finally, the proposed TVERI framework is a conceptual model based on the organization of the current evidence and should be regarded as a hypothesis-generating tool, which will require future theoretical development and empirical testing before possible implementation

3 Ecological determinants of viral emergence

3.1 Biodiversity, reservoir host dynamics and viral emergence

Tropical ecosystems are home to a high degree of biodiversity, so they influence zoonotic virus emergence in a complex way. From one side, biodiversity always means a higher chance of demonstrating heterogeneity in viral properties and species carrying viruses. The notion of biodiversity gave rise to the “dilution effect” and the “amplification effect.” On the one hand, more diverse ecosystems demonstrate the abundant richness of viruses and animals carrying them. It may reduce disease spread, as many species would have a low ability to carry the pathogen. On the other hand, destruction of the ecosystem and loss of biodiversity give rise to a singular host population of one species that will be very effective in transmitting the pathogen (9, 10). Therefore, the role of biodiversity in the emergence of viruses should be viewed adequately through the lens of structural changes of ecosystems, host populations, and anthropogenic impact, which resulted in disturbance of the ecosystems with the loss of biodiversity. In the One Health framework, you should consider spillover (animal-to-human transmission) and spillback (transmission from human to animals) when evaluating viral emergence. Although spillover is regarded as the most important mechanism of the emergence of new zoonotic viruses, there is growing evidence that spillbacks help establish new wildlife reservoirs and affect the evolution of viruses and long-term control methods of diseases (16, 17).

3.1.1 Characteristics of bat viromes

The Chiropterans (bats) have been identified as one of the best wilderness hosts of emerging diseases, owing to their specific phenotypic properties such as diversified species, worldwide habitat and long lifespan, as well as their social aspect of sleeping (10, 18). According to metagenomic studies, the bats possess various viruses representing Paramyxoviridae, Filoviridae, Coronaviridae, and Rhabdoviridae families, as well as other species associated with viral processes (18). There are different theories explaining the highly competent reservoir functions of bats. It appears that bats are significantly different as far as DNA repair efficiency, inflammatory response pathways, and presence of various effector immune mechanisms are concerned (19, 20).

The distinctive relationship that bats have with viruses allows them to harbor viruses for lengthy periods of time while occasionally releasing active virus particles into their surroundings. Shedding of the viruses is amplified during what are thought to be ecologically stressful situations like food scarcity and habitat disruption, together with issues tied to the rainy season and pregnancy and lactation of female bats, leading to greater chances of the virus spillover into domestic animals or humans. An instance of ecological processes is presented by the Nipah virus discharge. Fruit bats belonging to the genus Pteropus have viruses continuously in their system without becoming ill, discharging the virus with their saliva, urine, and birth liquids. By heightening contact between bats, domestic animals, and people, activities such as farming and destruction of nature enhance viral transmission across species (21, 22).

3.1.2 Rodent reservoirs

Rodents are the second largest group of animals that are known to transmit zoonotic viruses. There are over 2,200 different kinds of rodents, which occupy different types of habitats in the tropical and subtropical areas (16). The rodents are known for their high rate of reproduction and adaptability to the environment as well as their close relationship with human activities, which helps in the continuous spread of the viruses. However, contrary to bats with long-term and persistent infections, rodents are productive not through long-term infections, but through continuously changing their population (17). Rodent-borne viruses, such as hantaviruses, arenaviruses, and mammarenaviruses, are known to have an exclusive affinity for certain hosts as a result of co-evolution with their rodent hosts (23). Nonetheless, factors such as environmental changes, agricultural development, and urbanization, as well as climate-driven habitat changes, can bring changes to the ecological balance and thus increase the chance of viral spillover to humans (24). One prominent example is the Lassa virus, which is maintained in the multimammate rat (Mastomys natalensis) throughout West Africa, causing human infection through contaminated food, surfaces, and excretion (25). Therefore, effective interventions against viral emergence should involve not only rodent control but also modifications in terms of sanitation, heating, and storing food supply, as well as One Health monitoring (26).

3.1.3 Non-human primates and avian reservoirs

The influence of non-human primates as significant species in the history of the evolution of different human viral pathogens is well-known. Simian immunodeficiency viruses (SIVs) have been associated with African primates for thousands of years, and multiple incidences of zoonotic transmission have led to the emergence of HIV-1 and HIV-2 in humans (27). Factor such as forest fragmentation, habitat encroachment, bushmeat hunting, and increased interaction between humans and wildlife have created more chances for physical exposure to infected blood and tissues, which has facilitated the transmission of viruses (28).

Wild aquatic birds, species such as the orders Anseriformes and Charadriiformes, are natural reservoirs for avian influenza viruses. Seasonal migration allows aquatic birds to spread the different varieties of the influenza virus across continents and connect tropical, subtropical, and temperate ecosystems (29). In addition to being passive carriers, migratory birds aid in the evolution of viruses by introducing new strains of viruses to novel ecosystems where their interaction with domestic birds can facilitate the reassortment of the viruses and creation of new strains (7).

3.1.4 Amplifier host and cross-species transmission

The occurrence of viruses frequently entails intermediate or amplifier hosts that facilitate transmission between wildlife reservoirs and people. Domestic animals play a crucial role in One Health as they increase contacts between wildlife and livestock and people (30). Swine are one of the best-studied amplifier hosts because they can get both avian and mammalian flu viruses. Co-infection with different strains of the flu may cause virus reassortment and the creation of new strains capable of causing pandemics. Therefore, pigs are known as the important “mixing vessels” of the flu (30).

The emergence of the Nipah virus in Malaysia highlights the significance of amplifier hosts in viral emergence. Fruit bats transmitted the Nipah virus to intensively farmed pigs, where the virus multiplied effectively before further spreading to humans (31). On the contrary, the epidemiology of Nipah in Bangladesh is quite different. Most of the cases of human infection happen as a result of direct transmission from bats during the consumption of contaminated date palm sap, rather than via intermediate livestock hosts. This example indicates that the ecological conditions, agricultural practices, and cultural customs jointly contribute to the emergence of viruses in various tropical regions (32).

3.2 Climate change and environmental disruption

Climate change affects viruses’ emergence through various complex interactions involving vector ecology, wildlife hosts, viral replication, and environmental change (24). While tropical regions exhibit constantly elevated temperatures suitable for vectors and viruses’ year-round activities, more recent research indicates that many temperate regions are where the highest rate of global warming has been observed. At the same time, even minimal changes in temperature in tropical ecosystems can significantly change how many viral vectors are present, how they transmit viruses, and how they interact with their hosts because many tropical vectors are already on the edge of reaching their greatest thermal limits (7, 33). Thus, it is important to understand climate change not merely as a factor of temperature increase, but also as a factor of the ecological changes that reshape pathogen transmission in many ecosystems.

3.2.1 Vector expansion and contraction

Temperature is a determining factor in vector competence, survival, biting rate, and the extrinsic incubation period of many arboviruses (32). Aedes mosquitoes, the main vector for dengue, chikungunya, Zika, and yellow fever viruses, demonstrate their efficacy primarily within a certain temperature range. Slightly elevated temperatures will boost the process of viral replication, leading to shortening of the extrinsic incubation period of arboviruses, while significantly high temperatures will result in reduced longevity of mosquitoes along with elevated rates of viral replication (32). In addition to changing the altitudinal distribution of mosquitoes, climate change has also affected their geographical distribution. In tropical climates, Aedes mosquitoes have colonized regions at high altitudes such as the Andes, East African Highlands, and Himalayan foothills; thus, Aedes invaded populations that were previously not exposed to arboviruses (34). At the same time, increased temperatures have allowed for gradual extension of Aedes populations outside tropical zones to southern areas of temperate regions, including some places in Europe and America, which led to heightened risks of arbovirus emergence and transmission. All of the above-mentioned show that climate-derived expansion of vectors is no longer limited to tropical ecosystems.

3.2.2 Precipitation variability and ENSO

The aspects of rainfall heavily control the amounts and availability of Aedes mosquito breeding sites (35). Both too much rainfall and long-lasting drought have been shown to raise transmission of viruses due to different ecological impacts. While heavy rains create many temporary breeding habitats, drought conditions are often responsible for the establishment of good water storage practices in households that would create new breeding grounds for different Aedes mosquitoes. As a result, the associations between precipitation and the transmission of arboviruses are complex and highly situation-dependent (35).

El Niño–Southern Oscillation (ENSO) is believed to form one of the key aspects of climatic variations in tropical regions. It molds the local temperature, precipitation, humidity, and vegetation processes, which are linked to the abundance of mosquito species and viral transmission (36). The use of various predictive models that include climate factors related to ENSO has proved a success, as outbreaks of dengue fever have been predicted ahead of time dozens of times proofing great efficiency of such a climate-driven monitoring system (36).

3.2.3 Deforestation, forest fragmentation, land-use change and urbanization–

Land-use change and deforestation are important ecological factors in viral emergence, as they change the interactions of wildlife, domestic animals, and humans with each other (33). Deforestation worldwide is around 10 million hectares every year, leading to habitat degradation, extinction of species, and more animals coming into contact at the interface of wildlife, livestock, and humans (33). Deforestation does not occur in isolation but simultaneously with agricultural expansion, road building, mining, and urbanization, creating entirely new ecological conditions for virus transfer in nature.

Forest fragmentation can be discussed as another process in ecology that requires separate attention. Unlike complete loss of the forest, forest fragmentation allows states to separate forests into smaller and isolated patches of habitats, which become surrounded by agricultural or urban areas. Habitats of this type make it possible for wildlife species to stay close to human settlements, increasing the edge effect, changing the vector community, and making it possible for animal, domestic, and human hosts to come into contact with each other (37). For this reason, forest fragmentation is reported to have facilitated the emergence of viruses in the majority of tropic ecosystems, though the effects produced may vary in different ecosystems based on biodiversity, host structure, and landscape.

The process of agricultural conversion has considerably changed tropical ecosystems, especially in Southeast Asia, as extensive oil palm farming and agriculture have changed the habitats of many animal species and the distribution of reservoir hosts (37). Certain shifts in land use may be to the advantage of adaptable reservoir species such as bats and rodents while reducing the overall ecological richness of the environment; thus, the number of suitable hosts thereby increases. This exemplifies how the decline of biodiversity can promote the virus transmission in some environmental conditions.

The 1998–1999 Nipah virus outbreak is one of the most striking illustrations of disruption of ecology that caused a new virus to emerge (38). Deforestation, prolonged drought caused by El Niño events, growth of intensive pig farming, and the installation of fruit orchards near pig farms contributed to the change of bat foraging behavior and increased the amount of interaction between fruit bats and pigs. Pigs then acted as amplifier hosts and transferred Nipah virus to humans, showing that despite being separate risk factors for emergence of a virus in humans, the factors closely work together in one scheme (38).

Rapid urbanization modifies dynamics of viral emergence due to higher population density, increased peri-urban settlements, and the creation of advantageous habitats for mosquitos due to mismanagement of waste and water. Urbanization also leads to the development of many interfaces between wildlife and domesticated animals, which increases the chances of zoonoses and vector-borne diseases. Thus, preventing future incidence of viral infections in humans involves integrated land use planning, conservation of biodiversity, sustainable urban development, and One Health surveillance, instead of relying only on individual measures.

3.3 Agricultural intensification, wildlife trade and cultural practice

livestock intensification

Livestock intensification, with a primary focus on Concentrated Animal Feeding Operations (CAFOs), has considerably modified the ecology of infectious diseases while creating opportunities for the emergence of new viruses (39). The high population density of animals, a small number of genetic varieties, frequent relocation of animals, and ongoing cycles promote effective viral replication, survival, and actualization of evolutionary changes. These production systems create further conditions for viral mutations and interspecies transmission, especially in the case of low levels of biosecurity.

In Southeast Asia, CAFOs aimed at hog farming can host thousands of animals despite the limited space, thus having a considerable number of hosts for the ongoing transmission of viruses (40). Pigs are vulnerable to both bird and mammal viruses, thus working as “mixers” that lead to the chance of the emergence of a new strain of the virus that can start pandemic development. This demonstrates the importance of the integration of livestock management strategies, veterinary monitoring, and biosecurity measures in a One Health concept.

3.3.1 Wildlife trade and wet markets

Both traditional wet markets and the live animal trade continue to be crucial ecological interfaces where wildlife, domestic animals, and people have regular interactions (41). Many animals from several regions are sold in crowded situations, which can help bring viruses from wild animals to human populations. There is bad hygiene, an absence of sufficient animal health monitoring, and constant mixing of species, which escalate the risks.

The case of SARS-CoV is a well-researched example of such an occurrence. Before the infection of humans, masked civets played the role of key amplifying hosts in live animal markets, and although bats are known as the main natural reservoir (42), this case shows how wildlife markets and animal trade can create unprecedented transmission channels that cannot occur in a natural environment.

3.3.2 Cultural practices and human-wildlife interfaces

Cultural and occupational practices can increase human-wildlife interactions and thus influence the emergence of viruses, besides agricultural intensification and wildlife trade. The case of Bangladesh is well known due to the traditional use of fresh date palm sap. Fruit bats (Pteropus spp.) usually contaminate sap collection containers with their saliva and urine when they feed on sap, allowing the bats to transmit the Nipah virus to humans directly (43).

The example shows that ecology is not the only factor influencing viral emergence because of the important role of culture in human behavior. Thus, public health interventions must be culturally appropriate, and community education and locally adapted One Health monitoring should be conducted to decrease the risk of spillover while taking into account existing cultural practices (Table 1).

Table 1. Major emerging viruses in tropical regions: ecological drivers and reservoir hosts.

4 Molecular determinants of viral adaptation

4.1 Viral genetic plasticity

RNA viruses have incredibly high mutation rates, which are measured by error rates that vary from 10^-3 to 10^-5 nucleotide substitutions per replication cycle (44). This high evolution of RNA viruses is mainly due to a lack of proofreading ability by most RNA-dependent RNA polymerases, which results in rapid acquisition of variations (45). It is this feature that allows RNA viruses to adapt effectively to changing environmental conditions and escape the immune reactions of the host organisms, as well as cross over the species barrier, thus serving as a basic molecular factor of viral emergence (Figure 3).

4.1.1 Mutation rates and quasispecies

RNA viruses exist as quasispecies, consisting of various genetically different yet closely similar varieties of viruses that adapt through natural selection (46). Quasispecies is not a collection of viruses with the dominant genome but rather a constant source of mutants enabling some viruses to escape adverse conditions. The adaptive ability of these viruses includes better tissue tropism, the ability to avoid immune system response, antiviral resistance, and adaptation to the host organism (47).

Quasispecies emergence can be illustrated by the development of the so-called variants of SARS-CoV-2. Mutations accumulated in the spike protein and other genome portions allowed the formation of the so-called variants with different transmissibility, ability to escape immune response, and antigenic properties, which displays that the continuous process of virus evolution significantly impacts the process of epidemics (48).

4.1.2 Recombination and reassortment

RNA viruses also increase their genetic variation through recombination and reassortment apart from point mutation. Recombination happens when the RNA polymerase of a virus starts using a different template during the process of genome duplication, thus producing hybrids formed from two or more parent viruses (49). Coronaviruses have high rates of recombination, and it helps them rapidly obtain beneficial genetic characteristics that can adapt them to their environments (50). Nevertheless, reassortment occurs in viruses that have segmented genomes like the influenza viruses (51). When two different strains of influenza virus simultaneously infect one host cell, they can exchange entire genomic segments, generating new strains of viruses with new antigenic properties (52). The history of pandemic influenza demonstrates how reassortment can give rise to novel viruses with new antigenic properties from avian, swine, and human strains that may transmit efficiently among humans and emphasizes the significance of animal reservoirs as a source of pandemics.

4.1.3 Genetic determinants of host range

The evolution of the host range and the ability to transmit viruses from animals to humans depend greatly on certain genetic characteristics of viruses, which influence how they recognize their receptors and different hosts. For example, in the case of influenza viruses, the hemagglutinin (HA) is responsible for the choice of a receptor, since it allows the viruses to recognize α2,3-sialic acid receptors in birds and α2,6-sialic acid receptors in mammals (53). A similar effect can be observed in coronaviruses, which acquire mutations in their spike glycoprotein that increase their affinity for mammalian receptors and allow them to adapt to new hosts. An example of this can be the effect of the mutations D614G and N501Y, which enable coronaviruses to bind to human ACE2 more effectively and become more infectious. In sum, these adaptations are clear evidence of how minor genetic changes may increase zoonotic potential and lead to the emergence of viruses in humans (54).

4.2 Host receptor adaptation

To demonstrate successful completion of zoonotic transmission of viruses, it is essential for the viruses to surpass certain barriers and obstacles at the cellular level found in the hosts (55). In other words, the success of cross-species transmission relies heavily on one of the most important factors affecting zoonosis, that is, the receptor recognition element of that whole process (56). The key point is that one cannot consider viral adaptability without taking into account its ability to mutate and improve its receptor-binding proteins, therefore allowing the virus to enter the host organism and reproduce.

4.2.1 ACE2 receptor adaptation

Several coronaviruses use the angiotensin-converting enzyme 2 (ACE2) receptor to enter host cells, including SARS-CoV, SARS-CoV-2 and HCoV-NL63 (57). The presence of genetic variability in ACE2 within mammalian species affects viral host range and susceptibility, which has an impact on the occurrence of interspecies transmission (57).

The occurrence of adaptive mutations in the SARS-CoV-2 spike protein has contributed to higher binding efficiency of the virus to human ACE2 and its increased success in transmitting to human hosts (58). This leads to the conclusion that the evolution of receptor binding is an ongoing process in evolution because of natural selection and not just one-time mutation.

Henipaviruses, e.g., Nipah virus, use the conserved ephrin-B2 and ephrin-B3 receptors, which are widely present among mammals (59). The broad presence of the above-mentioned receptors among species explains well the wide host range of henipaviruses, such as bats, pigs, dogs, horses, and humans (60). But even though the receptors are conserved, it does not mean that the pathogenicity will be compatible. The structure of glycoproteins of the virus, the immunity of hosts, and the ecological context should be considered together.

4.2.2 Sialic acid receptor specificity

Influenza viruses show a distinct host affinity by the selective binding of the different sialic acid receptors by the HA protein (61). Avian influenza viruses preferentially attach to α2,3-linked sialic acid receptors; on the other hand, human influenza viruses identify α2,6-linked sialic acid receptors in high-order (62). Pigs express both of the known receptor forms in their respiratory tract, and hence they prove their role as important “mixing vessels” and enable infection with both avian and human viruses and provide ample chances for the exchange of RNA (63). The mutations in some important amino acids such as amino acids 226 and 228 in the HA protein that determine its receptor specificity cause changes in receptor recognition and consequently affect host adaptation and pandemic potential (63).

4.2.3 Host protease activation

The binding of the receptor does not constitute a sufficient condition for a productive infection to take place. Viral proteins need to undergo activation by host proteases to permit their fusion with cell membranes and the entrance of the virus into cells (64). In general, cleavage of viral proteins can be seen as an additional biologically relevant factor determining both the tissue tropism and the ability of a virus to cause a disease. Viruses that cause avian influenza are characterized by the presence of multiple basic amino acids in their cleavage sites that furin-like proteases can recognize. Hence, virus infections can spread widely throughout the infected organisms (65). The disease caused by Ebola virus is the result of cleavage of viral glycoprotein with the help of endosomal cathepsins before it undergoes fusion (65). In other words, both adaptation of receptors and utilization of host proteases define if a virus is able to infect, having crossed the species barrier.

4.3 Immune escape mechanism

Viral outbreaks are determined not only by the ability of viruses to infect new hosts but also by the effectiveness of the virus in evading innate and adaptive immune responses. RNA viruses use various immune escape mechanisms that inhibit antiviral responses concerning signaling, modify cytokine responses, and circumvent immunological memory, which increases the chances of viral transmission and the severity of the disease (66).

4.3.1 Interferon antagonism

The type I interferons (IFN-α and IFN-β) are the first step in innate antiviral defense, which prevents virus replication and activates anti-viral genes (66). As a result, the emergent viruses have developed gene products that inhibit interferons or interferon signaling, allowing robust replication during the early stages of infection. The influenza virus possesses the NS1 protein, which prevents the activation of the RIG-I pathway, inhibits processing of host mRNA, and reduces interferon production (67). Similarly, paramyxoviruses possess V proteins which degrade the STAT proteins and inhibit JAK-STAT signaling, in this way evading the effect of the interferon-mediated immune system responses (43). These means impede the development of the antiviral immune responses of the host and make it possible for viruses to establish themselves after spillover (Table 2).

Table 2. Immune dysregulation signatures in major tropical viral infections.

4.3.2 Cytokine modulation

In addition to their actions against interferons, some viruses are known to exploit the host’s cytokine networks for immunopathology and persistence (68). For example, glycoproteins of the Ebola virus cause significant apoptosis of lymphocytes through the activation of the Fas-FasL signaling pathway and thus lead to marked lymphopenia, although not many lymphocytes are infected directly (69). Similarly, the Nipah virus hampers the regulation of cytokine production by inhibiting antiviral responses in the early phase but activating the synthesis of pro-inflammatory cytokines later on through hyperactivation of the immune system (70). The consequence of such a mismatch between the two types of responses contributes greatly to the poor outcomes in various neurological conditions.

4.3.3 Antigenic variation and immune memory

The flexibility of RNA virus genetics permits the development of new forms of viral antigens at any moment, increasing the probability of evading the neutralizing antibodies produced thanks to infection or vaccination (71). Antigenic drift is caused by the mutation of hemagglutinin (HA) molecules in the influenza virus, so vaccine modifications are periodically necessary. At the same time, special types of antigenic shifts caused by genetic mixing among different kinds of viruses may result in pandemic viruses (72). Even though coronaviruses have limited proofreading capabilities, mutations in the crucial areas of antigens have shown that those viruses are able to partially escape from the immune system of people who have already suffered from a virus infection (73).

At the same time, the process of viral emergence may be influenced by the presence of the adaptive immune memory and the cross-protective immune response. It is generally accepted that T-cell cross-reacting response and broadly neutralizing antibodies produced after the exposure to similar viruses might protect a person from the newly appearing virus.

5 Host – pathogen interaction and immune dysregulation

5.1 Innate immune recognition

The innate immune system is the first layer of the defense mechanism against viral attack and is crucial in deciding whether spillover viruses can lead to the establishment of viral infections in a new host. The immediate detection of viral elements triggers defense mechanisms, but late and defective innate immunity can lead to high amounts of viruses, serious symptoms of the disease, and increased possibility of transmission (74).

5.1.1 Pattern recognition receptor

The pattern-recognition receptor (PRRs) family recognizes conserved pathogen-associated molecular patterns (PAMPs) in viruses. For instance, toll-like receptors (TLRs) in the endosomal compartments—TLR3 recognizes double-stranded RNA, while TLR7/8 identifies single-stranded RNA, and TLR9 detects CpG immunogenic DNA—combined with cytoplasmic RIG-I-like receptors (RIG-I and MDA5) are responsible for the identification of viral genomes and intermediates (75).

In particular, during varieties of infection, the presence of the virus’ RNA is detected mainly by RIG-I and MDA5 in dendritic cells and macrophages, which allows for an early initiation of the immune response (76).

5.1.2 Interferon induction and antiviral signaling

The ability to recognize viral nucleic acids enables the start of the signaling processes which involve IRF3, IRF7, NF-κB etc., resulting in the synthesis of the type I interferons (IFN-α and IFN-β) (77). The interferons are released outside the cell, where they attach to the receptor for interferon-α and β (IFNAR) elicits the activation of the JAK-STAT pathway, which results in the production of hundreds of the interferon-stimulating genes (ISGs) being active in the process of viral replication suppression (78). Thus, the adequate production of interferons defines the outcome of the disease, with many of the viruses being able to avoid this signaling pathway during the initial period of infection and implement the replication process before the system of adaptive immunity can respond. Delayed interferon production was shown to correlate with the severity of the disease in a number of recently discovered viruses.

5.1.3 Natural killer cell response

Natural killer (NK) cells are critical in the innate immunity response against viruses, as they can kill infected cells even before adaptive immunity enters the picture (79). They identify infected cells by using “missing-self” strategies, which involve identifying the downregulation of major histocompatibility complex class I (MHC-I) after viral infection. In severe viral infections, such as COVID-19, the inefficiency and low activity of NK cells are found to be responsible for the severe viral replication (80). Taken together, the roles of pattern recognition receptors (PRRs), interferons, and NK cells play a significant role in the innate immune system and determine the viral infection outcome and future adaptive immune responses.

5.2 Cytokine storm and immunopathology

The innate immune system activation is vital for restricting virus replication; however, the overdrive or inappropriate response of the immune system usually becomes the key reason behind the severity of the disease. In various newly discovered viral diseases, uncontrolled pro-inflammatory cytokine production (called “cytokine storm”) is the major contributor to tissue damage instead of the direct deleterious impact of viruses. Thus, the outcome of the disease significantly relies on how well the antiviral immunity and inflammatory regulation are synchronized.

5.2.1 Dengue immunopathogenesis

The infection of the dengue virus occurs in a wide spectrum, including inconspicuous disease to severe cases of viral hemorrhagic fever and regressive dengue syndrome (14). One of the most notable aspects of the severe case of dengue is through antibody dependent enhancement (ADE), where pre-existing antibodies lead to the entry of this virus into the Fc receptor-containing immune cells with the marked influence of heterologous serotypes (81). In fact, this interaction highlights the link between adaptive immunity and that of the innate immune system, causing massive replication of the virus as well as an unfathomable amount of inflammatory responses in the body.

In this case of severe dengue, one can observe the extremely raised levels of TNF-α, IL-6, IL-8 and IL-10 leading to rupture of the blood vessels, loss of plasma and consequently severe case of shock (82). Such observations clearly indicate that immunopathology is one of the reasons for the emergence of complication in patients rather than mere replication of the virus.

5.2.2 Chikungunya virus-induced chronic inflammation

Unlike the case of dengue, chikungunya virus is known to induce chronic inflammatory disease after the acute phase of infection (83). The presence of viral antigens in macrophages and fibroblasts leads to constant stimulation of the immune system and release of cytokines resulting in the development of chronic arthritis (84). The rise in concentrations of IL-13, MCP-1, and RANTES has been associated with the manifestation of chronic musculoskeletal disorders, whereas experimental investigation shows that macrophages as well as CD4⁺ T cells are responsible for inflammation of joints (84).

5.2.3 Ebola virus-induced immunosuppression

Ebola virus disease has led to severe immunological dysregulation. This means that there is both immune suppression and hyper-inflammatory responses to the infection. Viruses can produce a number of proteins such as GP and VP35, which in turn suppress antiviral immune responses and cause cell death in lymphocytes but limited viral replication in them. In advanced cases of Ebola virus disease, there are high levels of some inflammatory cytokines, including IL-1β, IL-6, and TNF-α (85). This causes systemic inflammation, endothelial dysfunction, and damage to multiple organs of the victim of the disease (86).

5.3 Chronic immune activation and viral persistence

Numerous new viral infections are acute and self-resolving, but some viruses have the capacity to cause prolonged immunological activation or can persist in those immunologically protected areas, leading to chronic clinical complications. Long-lasting inflammation following viral infection plays an essential role in the long-term morbidity and disease burden of the infection, and is also a major cause of morbidity in the aftermath of the acute disease.

5.3.1 Post viral syndromes

Several newly recognized tropical viruses have been found to lead to lasting immune activation following their infection. An infection from the chikungunya virus is well known to result in chronic inflammatory arthritis caused by viral antigen persistence in the macrophages and fibroblasts, which exist in connection with the affected joints as the result of continued immune activation and long-term cytokine production (87). Ebola virus can stay in immune-privileged sites, such as the eye, central nervous system, and testes, after apparent clinical recovery. Such situations can lead to uveitis and prolonged virus shedding in the semen, which stresses the necessity for post-recovery control measures and monitoring of victims (88).

5.3.2 Immunological sequelae and adaptive immune memory

Emerging viral infections can lead to changes in the immune system that last beyond the time of the active illness. The immune system’s constant work can cause chronic inflammation that disrupts the immune balance and affects vaccines and living organisms’ susceptibility to new infections (89). It is generally accepted that adaptive immunity protects but sometimes takes unexpected forms depending on how similar two viruses are. In this case, the immune memory could produce common T-cells, which provide some degree of protection against another related virus and lessen the negative impact of disease (71). However, it is worth noting that similar processes can lead to undesired results. The most popular example that demonstrates this is the case of ADE. Non-neutralizing or partially neutralizing antibodies from the primary infection would contribute to the spread of disease by allowing the virus to enter the cells that should have controlled them in the second case of infection with the neighboring serotype (81). Therefore, scientists worry about the consequences of the similar mechanism in the case of Zika and dengue, etc. (90).

5.3.3 Congenital Zika virus as an example of overlooked viral capacities

Besides immunological sequelae, viral emergence can also disclose previously unrecognized transmission capabilities. Congenital Zika virus infection is an example of a newly emerging virus that utilizes vertical transmission pathways to infect the fetal CNS, leading to permanent neurological and developmental abnormalities collectively called congenital Zika syndrome (90). This example shows that emerging viruses can possess unexpected pathogenic capacities, such as transplacental transmission and neurotropism, which are not related to adaptive immune memory but reflect the intrinsic biological properties of the virus and the susceptibility of certain host populations.

6 Integrated One Health case studies linking ecology, molecular adaptation and immunology

6.1 Case study 1: Nipah virus emergence in Bengali language

The emergence of NiV in Bangladesh highlights the complicated interplay between ecological disturbances, viral molecular changes, host immune responses and human behavior through the One Health approach. Ecologically, the Pteropus medius fruit bat contaminates raw date palm sap with its saliva and urine during feeding, providing a direct spillover route from wildlife to humans, without any intermediary species (43).

At the molecular level, Nipah virus G glycoprotein attaches efficiently to the highly conserved ephrin-B2 and ephrin-B3 receptors, resulting in multiple mammalian hosts and easy cross-species transmission. Nipah virus shuts down early signaling pathways of interferon by degrading STAT proteins and induces delayed inflammatory responses leading to severe encephalitis and high mortality.

In terms of one health, effective prevention measures include putting bamboo skirts in areas of date palm sap collection, educating communities on not consuming raw sap, ecological monitoring of bat populations, and enhanced laboratory surveillance for early identification of outbreaks. The case testifies that by incorporating the dimensions of ecology, molecular monitoring, community engagement, and health preparedness, one can significantly minimize the risks of spillover.

6.2 Case study 2: dengue virus in urban Southeast Asia

The introduction of the dengue virus signifies a merging of urban ecology, vector biology, viral evolution, and the immune response of hosts. Urbanization, poor water management, and climate variability lead to better conditions for Aedes aegypti, which creates a problem with human-vector interactions. In molecular terms, the circulation of four dengue virus types increases genetic variation among the strains of the virus. According to immunology, secondary infection with a different virus type may lead to the syndrome (ADE) that will stimulate cytokine production, cause endothelial dysfunction, and cause blood pulmonary leakage and a severe form of the disease.

A complicated One Health approach should combine climate-based vector monitoring, integrated mosquito maneuvers, rapid identification of the virus type, social involvement in the fight against the disease, and upgraded clinical surveillance. The case studies provide an example demonstrating that viral emergence cannot be explained only with the use of ecological, molecular, or immunological approaches. Rather, the emergence of the virus is the result of the interaction of environmental, viral, immune, and human factors. These case studies prove the importance of the complex One Health model in determining, preventing, and combating the emerging viral diseases.

7 Translational diagnostic and molecular epidemiology

7.1 Genomic surveillance platforms

Nowadays, genomics plays a significant role in the detection of newly emerged viruses and the response to outbreaks. The new sequencing technologies allow us to detect the newly emerged pathogens, determine their evolutionary path, reconstruct transmission traces, and follow the variants in humans, animals, and the environment according to the One Health concept.

• Next generation sequencing application: The decreasing cost and portable nature of next-generation sequencing (NGS) have transformed tropical public health systems by enhancing their ability to test for viruses and monitor their spread (91). Metagenomic NGS allows for the unbiased detection of both previously known and new viruses in clinical, environmental, and reservoir samples. During the outbreak of Ebola in West Africa from 2013 to 2016, mobile sequencing laboratories were used to generate real-time genomic data to help make epidemiologic decisions about how to control the spread of the virus (92)
• Portable sequencing technologies: Portable sequencing technologies have made it easier to monitor viral genomes; Oxford Nanopore has enabled genomic surveillance to be performed with minimal capital investment, equipment that can be used in remote locations, and the ability to obtain results in real time (93). During the COVID-19 pandemic, Nanopore sequencing was used to rapidly monitor mutations of SARS-CoV-2 in areas of the world that have limited resources to conduct genomic surveillance. The integration of cloud-based bioinformatics systems allows the sharing of data globally and the ability to conduct real-time phylogenetic analyses on viral genomes (94).
• Wastewater-based epidemiology: Wastewater-based epidemiology is a method of monitoring the presence of viruses in a community through testing for viruses in the wastewater generated by that community, regardless of whether there are clinical facilities available in that community to conduct laboratory-based surveillance (95). The surveillance program implemented to eradicate polio in India was one of the first programs to use wastewater for surveillance of viruses; today, there are numerous examples of this type of environmental surveillance being used to detect viruses such as SARS-CoV-2 and other emerging viruses. Examples of the application of this type of environmental public health surveillance for viruses include the detection of dengue virus in the breeding sites of mosquitoes and the monitoring of Nipah virus in the habitats of bats in tropical countries (96).

7.2 Biomarker discovery

Biomarker discovery is becoming more and more important for early diagnosis, disease severity evaluation, treatment monitoring, and differential diagnosis of viral diseases. The integration of the biomarkers produced by the host and virus provides users with insights into the course of the disease and gives a chance for the application of precision medicine in the treatment of tropical viruses.

• Host transcriptomic signatures: Transcriptomic Correspondence to Host Response to Virus Infection: Host Responses to Virus Infection Impact Diagnostic and Prognosis Information Available through Transcriptomic Profiling (97). Dengue severity is associated with transcriptomic profiles, including increased interferon-stimulated genes early in the disease and activation of inflammatory genes prior to the onset of plasma leakage (98). Whole Blood Transcriptomics Provide Distinctions between Bacterial and Viral Infections.
• Cytokine Biomarkers: Multiplex cytokine biomarkers have provided prognostic signatures for dengue hemorrhagic fever, with increases in IL-10 and IL-1β and MCP-1 being associated with progression of disease, while increased levels of IL-6 and TNF-α correlate with severity of chikungunya arthritis (99).Acute phase proteins are readily measured and are accessible biomarkers, but there are limitations in specificity; therefore, care is required in the interpretation of data.
• Viral Load Dynamics: Predictor of Prognosis and Risk of Transmission. Quantitation of Virus Load will Provide Accurate Measurement of Prognosis and Predictive Capability of Risk of Transmission. Ebola Virus RNA Level Directly Correlates with Mortality (20) <20 Cycle Threshold Values Associated with > 80% Mortality Risk (100). Kinetics of DENV4 Viremia Will Vary Depending upon Serotype and Immune Status.

7.3 Point of care molecular diagnostic

Quick point-of-care (POC) diagnostics contribute to outbreak preparation through fast case identification and efficient clinical management and public health interventions, especially in economically disadvantaged tropical regions (101).Today’s technology includes both the molecular and antigen test-based diagnostic means, ensuring timely access to rapid testing.

• CRISPR-based detection: The detection of nucleic acids utilizing CRISPR-Cas systems has journeyed well beyond CRISPR’s original purpose for genomic editing with rapid, sensitive and specific viral pathogen diagnosis (102). This has been accomplished by combining isothermal amplification with CRISPR-mediated target cleavage utilizing either SHERLOCK or DETECTR platforms that provide either fluorescent or lateral flow output. Demonstrated applications include dengue, Zika, chikungunya and SARS-CoV-2 pathogen detection while utilizing minimal instrumentation (103).
• Isothermal amplification methods: Detection of nucleic acids utilizing isothermal amplification. Both loop-mediated isothermal amplification (LAMP) and recombinant polymerase amplification (RPPA) provide nucleic acid detection without the requirement to thermally cycle (104). Sensitivity of the RT-LAMP assay for the detection of dengue serotypes, chikungunya and SARS-CoV-2 exceeds that of RT-PCR. Additionally, lyophilized reagents can be developed and stored at room temperature, therefore negating the need for cold chain facilities.
• Antigen -based Point-Of-Care Diagnostics: Along with molecular diagnostics, rapid antigen detection tests are a crucial part of point-of-care testing. Though antigen tests often have lesser detection capabilities compared to nucleic acid amplification tests, they offer low-cost, fast and scalable screening during outbreaks. New innovations in technology such as nanomaterial-based biosensors, digital immunoassays and microfluidic methods enhance the detection sensitivity of these tests, paving the way for their utility in viral monitoring in tropical areas.
• Implementation Barriers: These barriers include regulatory approval, quality assurance of diagnostic assays, the dependability of supply chains and training of healthcare professionals to perform diagnostics (105). To establish successful POC diagnostic testing programs requires long-term investment in strengthening health systems (Figure 4).

8 Integrative One Health framework

8.1 The human -animal – environment interface

The concept of One Health, which acknowledges the interdependence of human, animal, and environmental health, highlights the role of all three in the processes of emergence, transmission, and persistence of viral diseases. Due to growing interactions between humans, domesticated animals, fauna, and vector arthropods in tropical ecosystems, there arise risks of not only zoonosis but also spillback, i.e., transmission from animal to human and back again. Such activities as bushmeat hunting, agriculture encroaching into forest territories, wildlife trading, feeding wildlife near houses, and the operation of live animal markets are believed to be high-risk interfaces. Understanding these pathways of bidirectional transmission is important for the development of integrated surveillance and prevention strategies in line with the concept of One Health (106) (Figure 5).

8.2 Integrated surveillance system

In order to carry out effective One Health surveillance, there is a need for coordinated monitoring of human, animal, wildlife, vector, and environmental health systems. Modern surveillance covers clinical, wildlife pathogen, vector surveillance, environmental sampling, wastewater-based epidemiology, and genomic surveillance that allow earlier identification of newly arising pathogens. The progressive emergence of the Nipah virus in Bangladesh demonstrates how using the integrated approach has proven itself. It means that bat ecological surveillance, date palm sap monitoring, community engagement, and molecular diagnostics all together enabled less human exposure and thus improved outbreak preparedness (107).

8.3 Predictive modeling

The combination of ecological, climate, molecular, epidemiological and socioeconomic studies has greatly aided predictive modeling of the emergence of viruses. The role of machine learning, artificial intelligence, remote sensing, satellite-derived environmental variables, and phylogenetic analysis is increasing in the identification of possible spillover hotspots and forecasting of outbreaks before the start of their widespread dissemination. However, predictive models are still dependent on the presence of well-organized surveillance results and require regular validation in various tropical ecosystems before the implementation in public health (108, 109).

8.4 The tropical viral emergence risk index: a proposed conceptual framework

To integrate the multiple ecological, molecular, immunological, and surveillance determinants discussed throughout this review, we propose the Tropical Viral Emergence Risk Index (TVERI), a conceptual framework intended to support systematic assessment of viral spillover risk in tropical settings. Importantly, TVERI should be regarded as a hypothesis-generating conceptual model rather than a validated predictive tool and therefore requires future empirical evaluation.

8.4.1 TVERI combines four component scores

TVERI = (E × 0.3) + (M × 0.3) + (I × 0.2) + (S × 0.2)

Where:

• E = Ecological Risk Score (deforestation rate, biodiversity loss, climate vulnerability, land-use change)
• M = Molecular Risk Score (viral family risk group, genetic plasticity, receptor adaptation potential, prior host jumps)
• I = Immunological Risk Score (population immunity, immune dysregulation markers, ADE potential)
• S = Surveillance/Diagnostic Readiness Score (genomic capacity, POC availability, health system strength)

8.4.2 Proposed theoretical scoring rubric

To standardize application, each domain score (0–10) is theoretically derived from composite sub-indicators. The Ecological (E) score considers deforestation rates (>5% annual loss = 8–10), biodiversity intactness indices, and climate vulnerability mapping. The Molecular (M) score is based on viral family risk grouping (e.g., Filoviridae and Coronaviridae scoring higher), genetic plasticity (e.g., mutation/recombination rates), receptor adaptation potential, and documented prior host jumps (≥2 = high score). The Immunological (I) score reflects seroprevalence indicating naïve populations, presence of immune dysregulation markers (e.g., cytokine storm propensity), and evidence of antibody-dependent enhancement (ADE). The Surveillance (S) score inversely reflects genomic sequencing density, point-of-care (POC) diagnostic availability, and health system strength (e.g., Global Health Security Index components). These theoretical assignments remain hypothesis-driven and are intended to be refined through future expert consensus (e.g., Delphi) and empirical calibration.

The weighting scheme was developed conceptually based on available evidence. Ecological disruption and viral evolutionary capacity are considered primary determinants of spillover. In contrast, immunological susceptibility and surveillance readiness primarily influence outbreak amplification and early detection. Consequently, ecological and molecular domains were assigned weights of 0.30 each, whereas immunological and surveillance domains were assigned weights of 0.20 each. These weights are hypothesis-driven and should be refined through expert consensus, sensitivity analyses, and empirical validation using retrospective and prospective datasets.

Each domain is assigned a score ranging from 0 (very low risk) to 10 (very high risk), based on available ecological, molecular, immunological, and surveillance evidence. These domain scores are intended to provide a standardized conceptual framework for comparing relative emergence risks rather than absolute quantitative predictions.

8.4.3 Illustrative retrospective application

To illustrate the potential application of TVERI, retrospective scoring was performed using several well-characterized viral emergence events. These examples are provided solely for conceptual illustration and should not be interpreted as empirical validation or predictive testing of the proposed framework (Table 3).

Table 3. Illustrative retrospective application of the tropical viral emergence risk index (TVERI) to selected viral emergence events.

Future versions of TVERI may also incorporate spillback risk, vector dynamics, socioeconomic determinants, and additional surveillance indicators to provide a more comprehensive One Health assessment of viral emergence.

8.5 Limitations and future directions

This review has certain flaws. The first limitation is that it is a narrative review instead of a systematic review; therefore, the selection of literature may suffer from selection bias, albeit the search strategy is comprehensive. The second limitation is that the framework proposed as TVERI is only conceptual and still needs empirical, statistical, and prospective validation. The third limitation is that the method for weighting and scoring is based on hypotheses and should not be treated as an evidence-based quantitative assessment. The fourth limitation is that different levels of surveillance capacity and availability of data on tropical regions may hinder the generalizability of the presented framework.

Examples presented in this article are just used as illustrations of information that can be analyzed using the TVERI framework but do not represent the validation on the predictive efficiency of this model. Further research has to analyze its applicability using multicountry data, expert Delphi consensus, sensitivity analysis, machine learning for optimization of weightings and data collection, and prospective research on outbreaks and their causes.

9 Research gaps and future direction

• Understudied tropical reservoirs: Many viruses that hide out in nature have never been looked for in the tropical reservoirs of various species. Bats alone are thought to be home to more than 3,000 different yet-to-be-discovered coronaviruses (110). We need to start doing systematic surveys on a large scale of tropical areas of the world as well as a large number of different species.
• Immune-genomics correlates: This area should be studied to find out if there are any specific immune genetics that determine if a person is susceptible to a particular disease and their outcome once they have contracted it. Also, if we can find out these specific genes in tropical populations using genome-wide association studies, then we should be able to use this knowledge to develop targeted interventions (111).
• Predictive AI modeling: There is considerable potential for the use of artificial intelligence (AI) to bring additional sources of data together to create better early warning systems for pandemic viruses. The challenge will be to validate these predictive models within a diverse range of tropical environments in order to create actionable responses by public health authorities (112).
• Vaccine platform gaps: As it currently stands, there is a significant gap between current platforms for the production of vaccines against coronaviruses and influenza and the development of vaccines against other virus families (for example, paramyxoviruses, filoviruses, and bunyaviruses) that might be candidates for causing pandemics (113). Therefore, there must be a significant investment into the technologies required to allow for rapid response rates against newly emergent viruses.
• Implementation science: In tropical communities, we must engage in implementation research to study the processes that impede the implementation of existing public health strategies, i.e., surveillance data, diagnosis technologies, and predictive models, so that we can ultimately improve the health outcomes of these populations (114).

10 Policy recommendations and translational priorities

The prevention and preparedness of emerging viral infections in tropical settings require policies that address the interconnected ecological, molecular, diagnostic, epidemiological, and health-system determinants of viral emergence. These priorities are particularly important in tropical regions where substantial differences exist in surveillance infrastructure, laboratory capacity, genomic sequencing, diagnostic access, trained personnel, and health-system resources. Accordingly, policy priorities should focus on strengthening One Health surveillance, reducing inequities in diagnostic and genomic capacity, improving preparedness through evidence-informed risk assessment, and translating scientific advances into sustainable public health practice (Table 4).

Table 4. Tropical-specific challenges for viral surveillance and control.

10.1 Strengthening integrated One Health surveillance

• Governments and public health authorities should establish or strengthen integrated surveillance systems linking human, animal, wildlife, vector, and environmental health data to facilitate earlier recognition of potential viral spillover events.
• Surveillance programs should prioritize high-risk interfaces, including areas affected by deforestation, agricultural expansion, wildlife harvesting, intensive animal production, and frequent human–wildlife or livestock–wildlife interactions.
• Surveillance capacity should be strengthened in resource-limited tropical regions where deficiencies in laboratory infrastructure, epidemiological reporting, and diagnostic access may delay the detection and characterization of emerging viruses.

10.2 Reducing inequities in genomic and diagnostic capacity

• National and international investments should promote equitable access to genomic sequencing, bioinformatics infrastructure, molecular diagnostics, and trained personnel, particularly in tropical regions with limited surveillance capacity.
• Point-of-care and decentralized molecular diagnostic technologies should be evaluated and adapted for settings where conventional laboratory-based testing is constrained by limited infrastructure, unstable electricity supply, inadequate cold-chain facilities, or geographic barriers.
• Technology-transfer and capacity-building programs should prioritize sustainable local implementation and workforce development rather than dependence on short-term externally supported diagnostic capacity.

10.3 Translating predictive risk assessment into preparedness

• Emerging viral risk assessment should integrate ecological, molecular, immunological, epidemiological, and surveillance indicators to identify settings in which enhanced preparedness may be warranted.
• The proposed Tropical Viral Emergence Risk Index (TVERI) may provide a conceptual structure for integrating these determinants; however, it should not currently be considered a validated predictive or resource-allocation tool. Its variables, scoring system, and weighting scheme require empirical evaluation using retrospective and prospective datasets.
• Future research should determine whether validated risk-assessment frameworks can improve the prioritization of surveillance, diagnostic preparedness, and preventive interventions in high-risk tropical settings.

10.4 Strengthening translational and implementation capacity

• Research and health policies should support implementation studies evaluating how genomic surveillance, molecular diagnostics, vaccination strategies, and other evidence-based interventions can be effectively incorporated into tropical health systems.
• Capacity-building programs should strengthen multidisciplinary expertise across veterinary medicine, public health, epidemiology, ecology, molecular virology, bioinformatics, and laboratory diagnostics.
• Community engagement and locally appropriate risk communication should be incorporated into prevention strategies, particularly where cultural practices, wildlife exposure, animal husbandry, and environmental changes influence viral spillover risk.

10.5 Promoting equitable international collaboration

• International collaboration should promote equitable access to scientific infrastructure, training, technology, and surveillance resources for countries with limited capacity to detect and characterize emerging viruses.
• Genomic, epidemiological, ecological, and environmental data sharing should be encouraged through appropriate scientific, ethical, legal, and data-governance frameworks.
• Long-term investment should prioritize sustainable local and regional capacity rather than relying exclusively on externally driven outbreak-response mechanisms.

Collectively, these policy priorities emphasize that reducing the risk of tropical viral emergence requires more than technological innovation alone. Effective preparedness depends on the integration of One Health surveillance, equitable access to genomic and diagnostic capacity, locally appropriate implementation strategies, community engagement, and sustained international scientific collaboration.

11 Conclusion

The presence of viruses in tropical areas is a result of the interdependence of three main aspects: ecological change, the evolutionary potential of a virus, and host immune system factors. The impact made by humans, like deforestation, loss of biodiversity, climate change, intensification of agriculture, and urbanization, changes the distribution of reservoirs and vectors, which leads to the creation of new spillover interfaces. At the same time, the ability of RNA viruses to change their genetic makeup leads to their adaptation to new hosts. The immune system can also help manage viruses; however, excessive inflammatory response may result in immunopathologies, which can lead to severe consequences of the disease and non-successful vaccine development.

This review emphasizes the necessity of a One Health approach that leverages ecological, molecular, and clinical indicators of risk at the same time. It introduces the Tropical Viral Emergence Risk Index (TVERI), which helps formulate hypotheses on the integration of these aspects into quantitative risk assessment. Nonetheless, TVERI is only a conceptual instrument that will need to be experimentally validated, subjected to sensitivity analysis, and tested before use. It needs to be further developed using expert consensus and machine learning optimization of weighting systems and testing of its adequacy.

The experience of the COVID-19 pandemic is illustrative of the destructive effects of viruses and rapid scientific response to such emergencies when capacity is readily available. Tropical countries have diverse ecosystems, high biodiversity levels, strong human impact, and underdeveloped healthcare systems and require investments in health surveillance systems, research, and health system upgrades.

Four strategic imperatives emerge from this synthesis:

• The predictive monitoring of various ecological, molecular, and clinical indicators must be conducted at the same time so that the required amount of different data can be combined with the help of AI and machine learning technologies. TVERI serves as a theoretical support for the final predictions based on this data, but it is extremely important to check the practicality of using the TVERI system based on the findings of the practical research.
• It is important to develop the infrastructure for genomic monitoring for the purpose of early detection of new viruses and organizing effective responses to the outbreaks, including improving the potential of the regions characterized by limited financial resources.
• Diagnostic technologies must be developed according to the special stress laid on their usability in regions with limited resources and on their heat-resistant and low-priced nature.
• Financial support for the research should be provided to solve the issues related to the application of discovered scientific knowledge in real-life situations.

An integrated, equity-based approach across ecology, molecular biology, immunology, diagnostics, social sciences and implementation science can improve global preparedness and reduce the risk of future pandemics originating from tropical regions. The systemic links between human, animal, and environmental health demand collective action across disciplines and sectors, with specific acknowledgement of the scientific and health inequities to be addressed in an effort to attain equitable pandemic prevention and response.

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Footnotes

Edited by: Thaneeya Duangchinda, National Science and Technology Development Agency Yothee Office, Thailand

Reviewed by: Sandra Laurence Lopez-Verges, Gorgas Memorial Institute of Health Studies, Panama

Kokouvi Kassegne, Shanghai Jiao Tong University, China