Hantaviruses as Emerging Zoonotic Pathogens: Molecular Biology, Epidemiology, Therapeutics, vaccine, and Pathogenesis

Hantaviruses are globally distributed zoonotic pathogens belonging to the family Hantaviridae and are responsible for two major human diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). Despite substantial progress in hantavirus research, important challenges remain in understanding the interactions among viral evolution, reservoir ecology, environmental change, transmission dynamics, and host immunopathology. This review provides an integrated One Health perspective that connects molecular virology and host-virus interactions with transmission ecology, global epidemiology, and the mechanisms underlying vascular leakage and severe disease. In addition to summarizing established knowledge, we highlight recent advances in hantavirus taxonomy, genomic and molecular surveillance, ecological and transmission modeling, and the identification of hantavirus circulation in previously underrecognized regions. Particular emphasis is placed on the role of reservoir host dynamics, climate and environmental change, habitat disturbance, and human-wildlife interactions in shaping spillover risk, as well as on endothelial dysfunction, immune dysregulation, and coagulation abnormalities as interconnected mechanisms of disease severity. We also identify persistent knowledge gaps concerning host susceptibility, viral persistence, determinants of differential virulence and tissue tropism, interspecies transmission, and the development of effective antiviral therapies and vaccines. By integrating these complementary perspectives, this review provides a framework for understanding hantavirus emergence and pathogenesis while identifying priorities for future surveillance, prevention, and therapeutic research.