Nipah virus: An exceptionally virulent emerging zoonotic pathogen

Nipah virus (NiV) is a highly lethal zoonotic paramyxovirus capable of human-to-human transmission; no vaccines or therapeutics are yet approved for clinical use. This review synthesizes recent advances in NiV epidemiology, virology, host immunity, pathogenesis, and countermeasure development to clarify key drivers of virulence and identify priority intervention targets.

We systematically searched PubMed from inception to 2026 using keywords covering NiV epidemiology, pathogenesis, immune evasion, vaccines, and antivirals, supplemented by hand-searching of reference lists. Two reviewers independently screened peer-reviewed studies, reviews, trials, and World Health Organization reports.

NiV exploits ephrin-B2/B3 receptors to mediate viral entry and evades host innate immune responses through both non-structural proteins (V, W, and C) and structural proteins. These strategies suppress RIG-I/MAVS, block STAT1/STAT2 nuclear translocation, and dysregulate NF-κB, thereby disrupting type I/II interferon (IFN-I/II) signaling. The resulting loss of innate immune control facilitates viral replication and systemic dissemination. Infection elicits neutralizing antibodies against the G and F glycoproteins and durable virus-specific CD4+ and CD8+ T-cell responses. Fatal outcomes correlate with high early viremia, delayed or insufficient antibody production, and dysregulated innate and adaptive immunity. In affected organs, notably the brain, a persistent CXCL10-driven cytokine storm recruits inflammatory infiltrates and amplifies immunopathological damage. Candidate vaccines (ChAdOx1 Nipah B, mRNA-1215, HeV-sG) and antivirals (nucleoside analogs, monoclonal antibodies, fusion inhibitors) are under clinical evaluation.

NiV pathogenicity arises from efficient replication, strong interferon antagonism, host immune dysregulation, cytokine-driven immunopathology, and widespread multi-organ damage. Urgent acceleration of effective vaccine and therapeutic development is needed.