Parahenipavirus langyaense (Langya virus): Spillover ecology, noncanonical receptor-mediated entry, and future control strategies.

Langya virus (LayV), classified in the species Parahenipavirus langyaense, is a newly identified zoonotic paramyxovirus discovered in febrile patients in eastern China in recent years. The discovery of LayV has expanded the field beyond the prevailing paradigm of highly pathogenic, bat-borne henipaviruses represented by Nipah virus (NiV) and Hendra virus (HeV), toward a parahenipavirus spillover model shaped by shrews, rodents, and agricultural ecological interfaces. Reported cases have mainly presented with fever, fatigue, cough, and vomiting, and may be accompanied by leukopenia, thrombocytopenia, and abnormalities in hepatic and renal function. However, owing to the limited number of cases, restricted surveillance coverage, incomplete follow-up data, and the lack of standardized serological tools, the true burden of infection, full spectrum of natural hosts, role of intermediate hosts, and animal-to-human transmission pathways remain unresolved. Sustained human-to-human transmission has not been confirmed. In recent years, accumulating evidence from viromic analyses of shrew lung tissues along the eastern coast of China, positive detection in the Ussuri white-toothed shrew (Crocidura lasiura) in South Korea, characterization of the LayV genome architecture, P-gene RNA editing, ELISA/multiplex RT-qPCR/CRISPR-Cas12a diagnostic platforms, and structure-based F/G antigen engineering and antibody development has begun to move LayV research from pathogen discovery toward mechanistic dissection and the construction of countermeasure platforms. In this Review, we systematically summarize the discovery of LayV, clinical features and epidemiological evidence, taxonomy and molecular evolution, animal host ecology, noncanonical receptor-mediated entry mechanisms, diagnostic approaches, and immunological intervention strategies. We further propose key research priorities centered on One Health surveillance, identification of the unknown receptor, structure-guided F/G antigen design, and integrated sampling across animal, environmental, and human populations.