Intrinsic and innate antiviral immunity against emerging viral infections: restriction factors, sensing pathways, and virus–host coevolution

Emerging viral infections continue to pose major challenges to global human and animal health, as highlighted by recent Mpox outbreaks, the COVID-19 pandemic caused by SARS-CoV-2, and ongoing outbreaks of African swine fever virus in domestic and wild pig populations. While much attention has focused on adaptive and systemic innate immune responses, intrinsic immunity represents a critical and often underexplored first line of cellular defense. This branch of host defense includes constitutively expressed or rapidly inducible restriction factors, including interferon-stimulated genes (ISGs) and other cell-intrinsic antiviral effectors, as well as intracellular sensors that detect viral proteins and nucleic acids soon after infection. These mechanisms can shape viral tropism, replication efficiency, transmission, and disease severity. At the same time, viruses evolve diverse countermeasures to evade, suppress, or exploit these defenses, including strategies that disrupt interferon-linked antiviral programs. A deeper understanding of intrinsic immunity and virus–host coevolution is essential for clarifying the biology of emerging pathogens and identifying new antiviral strategies.This Research Topic aims to bring together current perspectives and new findings on the role of intrinsic immunity in limiting, sensing, and shaping infection by emerging human and animal viruses. Despite rapid progress in the field, important questions remain regarding how restriction factors and intracellular sensing pathways influence early infection outcomes, how these responses vary across cell types and tissues, and how viral adaptation enables immune escape. Further questions concerns how intrinsic immune pathways intersect with interferon signaling and downstream ISG responses without being reducible to them. Recent advances in single-cell profiling, organoid systems, comparative virology, structural biology, and viral genomics now offer powerful tools to dissect these early host–pathogen interactions in unprecedented detail. By integrating mechanistic, translational, and evolutionary studies, this collection will help define how intrinsic immune pathways contribute to protection or pathogenesis, reveal conserved and virus-specific strategies of immune evasion, and identify opportunities for host-directed therapeutic development against current and future emerging infections.This Research Topic welcomes original research, reviews, and perspective articles addressing intrinsic immune responses to emerging human and animal viral infections. Relevant themes include, but are not limited to:• identification and characterization of antiviral restriction factors• intracellular sensing of viral nucleic acids and proteins• cell-intrinsic immune signaling networks• viral antagonism of intrinsic immune defenses• virus–host coevolution• determinants of species tropism and host range• tissue- and cell type-specific antiviral responses• the implications of intrinsic immunity for disease severity, persistence, transmission, and therapeutic intervention.Studies addressing the regulation or function of interferon-linked restriction factors and ISGs are welcome where they directly inform cell-intrinsic antiviral defense, intracellular sensing, or early virus-host interactions. Comparative studies across viral families, as well as translational work linking mechanistic insight to antiviral development, are also encouraged. Submissions that combine immunology, virology, cell biology, and evolutionary biology will be especially welcome. Topic editors: Bianca Schulte, Gyorgy Fejer Source: https://www.frontiersin.org/research-topics/83994/intrinsic-and-innate-antiviral-immunity-against-emerging-viral-infections-restriction-factors-sensing-pathways-and-virus-host-coevolution