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2036 Hantavirus: Molecular pathogenesis, immune evasion, clinical management, and emerging therapeutic strategies Microbes and Infectious Diseases
Abstract Hantaviruses are globally distributed, rodent-borne RNA viruses responsible for two life-threatening syndromes: hantavirus cardiopulmonary syndrome (HCPS) in the Americas, with case fatality rates of 35-40%, and hemorrhagic fever with renal syndrome (HFRS) across Europe and Asia, with mortality ranging from under 1% for Puumala virus to approximately 15% for Hantaan virus. Both syndromes share a common immunopathological core rather than directly destroying cells, hantaviruses infect vascular endothelial cells, sensitize them to vascular endothelial growth factor (VEGF)-mediated permeability, and suppress early innate immune defenses, thereby permitting high-titer viremia that precedes the CD8* T-cell-driven vascular leak responsible for clinical deterioration. The 2026 multi-country outbreak linked to the Andes virus and cruise ship travel has brought renewed urgency to a disease for which no approved antiviral exists, and no widely accessible vaccine has been licensed.This mini-review illustrates the molecular architecture of hantaviruses, multilayer interferon evasion strategies executed by the Gn cytoplasmic tail, nucleocapsid protein, and NSs nonstructural protein, and the endothelial pathogenesis model connecting B3-integrin tropism to VEGFR2 dysregulation and capillary leak. It surveys the clinical spectrum of HCPS and HFRS, current evidence for ribavirin and favipiravir, the critical role of extracorporeal membrane oxygenation (ECMO) in HCPS survival, and vaccine development from licensed inactivated vaccines in Asia to mRNA-platform candidates entering preclinical evaluation. Translational priorities discussed include point-of-care diagnostics, immunomodulatory intervention against CD8t-driven immunopathology, and accelerated clinical evaluation of vaccine candidates, with particular emphasis on Andes virus given its unique person-to-person transmissibility.