Human Organoid Models in Virology: Tools for Infection and Disease Research

Human organoid technology is transforming virology, developmental neuroscience, and neuroimmunology by providing three-dimensional, human-specific models of infection. Conventional animal models and immortalized cell lines often do not reproduce the cellular diversity, developmental cues, tissue architecture, or immune interactions of the human central nervous system. Congenital and postnatal infections caused by neurotropic viruses, including Zika virus, cytomegalovirus, herpes simplex virus, and emerging pathogens, can disrupt neural differentiation, cortical organization, circuit formation, glial function, and long-term brain health. Recent studies using human induced pluripotent stem cell-derived brain and neural organoids have demonstrated virus-specific effects on neural progenitors, neuronal survival, neurogenesis, synaptic development, and inflammatory signaling. However, major questions remain regarding developmental and age-dependent susceptibility, viral strain-specific pathogenicity, host genetic influences, organoid maturity, immune representation, experimental reproducibility, and the translation of organoid findings to clinical disease. Improved investigation is therefore needed to establish robust, physiologically relevant models that capture the interactions between viral pathogens and the developing human neuroimmune environment.This Research Topic aims to advance understanding of the neurodevelopmental and neuroimmune consequences of congenital and postnatal viral infections using human organoid models. It will examine how infection affects neural progenitors, neurons, astrocytes, oligodendrocytes, microglia-like cells, synaptic development, tissue organization, and brain maturation across developmental stages. Particular emphasis will be placed on viral entry, replication, dissemination, cell-type-specific tropism, innate immune activation, cytokine and chemokine signaling, microglial responses, blood–brain barrier dysfunction, neuroinflammation, and immune-mediated neural injury. The Research Topic will also explore how infection timing, viral strain, host genotype, sex, developmental stage, and prior immune exposure influence disease outcomes. By integrating virology, neuroscience, developmental biology, immunology, and neuroanatomy, it seeks to support the identification of biomarkers and the development of antiviral, neuroprotective, immunomodulatory, and regenerative strategies for infection-associated neurological disease.To gather further insights into the use of human organoid systems to investigate congenital and postnatal viral infections, this Research Topic will focus on experimentally validated neural and brain organoid models while recognizing limitations related to maturation, anatomical complexity, vascularization, immune representation, reproducibility, and clinical translation. We welcome articles addressing, but not limited to, the following themes:- Development, standardization, and validation of human brain and neural organoids for congenital and postnatal virus research- Viral entry, replication, dissemination, and cell-type-specific tropism in human neural organoids- Neurodevelopmental consequences of congenital viral infections, including altered neural differentiation, migration, synaptogenesis, and circuit formation- Postnatal viral effects on brain maturation, neuronal function, glial activity, and long-term neurological outcomes- Neuroimmune consequences of viral infection, including microglial activation, cytokine signaling, neuroinflammation, and immune-mediated neural injury- Interactions among viruses, neural cells, microglia, astrocytes, and other components of the developing neuroimmune environment- Modeling blood–brain barrier disruption, leukocyte recruitment, and peripheral immune–brain interactions- Age-, sex-, genotype-, and developmental stage-dependent differences in susceptibility and disease severity- Comparative studies of Zika virus, cytomegalovirus, herpes simplex virus, and emerging neurotropic pathogens- Multi-omic, spatial, electrophysiological, and advanced imaging approaches for characterizing infection-induced changes- Incorporation of vascular, immune, and barrier components into human organoid infection models- Antiviral screening and evaluation of neuroprotective, immunomodulatory, and regenerative interventions using human organoids- Structural and connectivity-level neuroanatomical consequences of viral neurotropism - mapping how neurotropic viral infection (e.g., Zika, CMV, HSV) disrupts cortical lamination, neuronal migration, dendritic architecture and circuit-level connectivity in human brain organoid models Topic editors: Dasja Pajkrt, Veronica Krenn, Patricia P. Garcez Source: https://www.frontiersin.org/research-topics/83241/human-organoid-models-in-virology-tools-for-infection-and-disease-research