Antigenic and structural insights into a Henipavirus attachment glycoprotein

The novel henipavirus, Langya henipavirus (LayV), was identified in China in 2022. The invasion of host cells by the henipavirus is facilitated through the interaction between viral attachment (G) and fusion (F) glycoproteins with receptors on the cell surface. The G proteins of LayV and Mojiang virus (MojV) exhibit high amino acid homology (86%), while they are located in a unique evolutionary clade within the Henipavirus genus. The crystal structure of the LayV G protein was resolved at a 3.4 Å resolution, revealing a head domain with six β-propeller-like domains and an absence of glycosylation modifications that is distinct from other henipavirus G proteins, such as those of Nipah virus (NiV) and Hendra virus (HeV). Furthermore, the prominent loop in the center cavity of the LayV G protein causes unique structural features. The LayV G protein was unable to bind to the existing henipavirus-neutralizing antibodies or the ephrin B2 receptors. Immunogenicity studies in mice demonstrated robust antibody responses elicited by the LayV G protein. These antibodies exhibited strong reactivity against both LayV and MojV G proteins. However, only weak cross-reactivity was observed with other henipaviruses. These findings underscore the need for tailored vaccines and therapeutics for LayV and related novel henipaviruses.