Enteroviruses and Severe Disease: Mechanisms of Neurotropism and Cardiotropism

Enteroviruses are among the most prevalent human pathogens worldwide, responsible for a spectrum of clinical outcomes that ranges from asymptomatic infection to life-threatening disease. While the vast majority of infections remain mild or self-limiting, a subset of individuals develop severe neurological problems, including acute flaccid myelitis, meningitis and polio or cardiac complications such as myocarditis and dilated cardiomyopathy. The molecular and cellular basis of this dichotomy remains incompletely understood: why do enteroviruses infect neurons and cardiomyocytes selectively, and what determines whether infection at those sites causes severe tissue damage or resolves without consequence?Recent advances in structural virology, single-cell transcriptomics, and organoid and iPSC-derived model systems have begun to reveal the host and viral determinants that govern tissue-specific pathogenesis. Understanding how these pathogens disseminate systemically, cross physiological barriers, such as the blood-brain barrier, and transit through neural and cardiac tissues has emerged as a critical frontier. Viral capsid structure, receptor tropism, innate immune evasion, and the interplay between direct cytopathic effects and immune-mediated injury have each emerged as critical axes along which neurological and cardiac outcomes are determined. Yet mechanistic understanding remains fragmented across model systems and enterovirus serotypes, limiting our ability to identify therapeutic targets or predict disease severity.This Research Topic brings together mechanistic and translational research focused on how enterovirus-host interactions drive severe neurological and cardiac disease. We seek contributions that define the viral and host factors underpinning neurotropism and cardiotropism, dissect the immunological and cell-biological mechanisms of tissue injury, and leverage advanced experimental models to bridge the gap between molecular mechanism and clinical outcome. The collection aims to establish a coherent mechanistic framework for severe enterovirus disease that can inform antiviral development, vaccine design, and clinical risk stratification.We welcome submissions organised around the following themes:1) Determinants of neurotropism and cardiotropism:Viral and host factors that govern the ability of enteroviruses to infect, replicate, and spread within the central nervous system and the myocardium. Topics include receptor identification and receptor-capsid interactions in neural and cardiac cell types; viral genetic determinants of neuro- or cardiovirulence; mechanisms of systemic dissemination and tissue invasion, including crossing of physiological barriers, such as the blood-brain barrier, retrograde or anterograde axonal transport, and immune-cell-mediated trafficking; intra-host evolution and quasispecies dynamics as they may influence tissue tropism; and surveillance data that directly link genomic variation in circulating strains to changes in neurological or cardiac disease.2) Innate and adaptive immune responses in severe disease: Host immune mechanisms that govern protection versus immunopathology in the CNS and heart. This includes innate sensing and interferon responses in neurons and cardiomyocytes; viral immune evasion strategies in these cell types; T cell and antibody responses; cytokine-mediated neuroinflammation and cardiac inflammation.3) Cellular and molecular mechanisms of tissue injury:How enterovirus infection leads to dysfunction and death of neurons and cardiomyocytes. Topics include direct cytopathic effects versus immune-mediated damage; viral manipulation of apoptosis, necroptosis, and pyroptosis pathways; metabolic reprogramming of infected cells; disruption of neuronal connectivity and cardiac function; and the long-term or post-acute consequences of severe CNS and cardiac enterovirus disease.4) Advanced model systems and translational insights:Experimental tools that enable mechanistic dissection of neurotropism and cardiotropism, assessed for their ability to recapitulate in vivo pathobiology. Topics include iPSC-derived neuronal and cardiomyocyte infection models; brain and cardiac organoids; humanised mouse models; ex vivo human tissue systems; and how insights from these models translate into antiviral strategies, vaccine platforms, or biomarkers of disease severity. Topic editors: Anna Majer, Soon Hao Tan Source: https://www.frontiersin.org/research-topics/81239/enteroviruses-and-severe-disease-mechanisms-of-neurotropism-and-cardiotropism