Hantavirus: biology, immune responses, and pathogenesis

Abstract The recent Andes virus (ANDV) outbreak on the MV Hondius cruise has raised global public health alarms due to its dangerous ability to person-to-person spread. Hantavirus infections primarily manifest as hemorrhagic fever with Eurasian renal syndrome (HFRS) and Americas hantavirus cardiopulmonary syndrome (HCPS), both characterized by endothelial manifestation. Two principal mechanisms, virus-mediated cytopathy and host-driven immunopathology, have been proposed to account for the pathological progression, while their interplay is yet to be fully explored. In this review, we synthesize the recent research on hantavirus biology, cellular entry mechanisms, and epidemiological characteristics, and particularly highlight that viral immune evasion and subsequent uncontrolled host immune responses act as the core pathogenic drivers. Hantaviruses employ diverse strategies to antagonize type I interferon signaling and autophagy, which delay early innate immune activation and enable extensive viral dissemination. The excessive activation of cytotoxic CD8⁺ T cells, natural killer (NK) cells, combined with functionally impaired regulatory T cells and dysregulated humoral immunity, initiates severe inflammatory cascades, which in turn disrupt endothelial barrier integrity and cause organ vasculopathy. We also outline current therapeutic and preventive strategies, along with key directions for future research. A better understanding of hantavirus immunopathogenesis will help develop improved countermeasures against this zoonotic disease.