Hendra virus attachment glycoprotein (HeV-G)

The Hendra virus attachment glycoprotein (HeV-G) is a critical surface protein of the Hendra virus, a highly lethal zoonotic paramyxovirus within the Henipavirus genus. HeV-G is a type II transmembrane protein that exists as a tetramer and is responsible for mediating the initial step of viral infection by binding to the host cell receptors ephrin-B2 and ephrin-B3, which are highly conserved across mammalian species [PMID: 23149603, PMID: 16142214]. This binding event triggers a conformational change in the associated fusion (F) protein, leading to the fusion of the viral and host cell membranes and the release of the viral genome into the cytoplasm. Due to its essential role in viral entry, HeV-G is the primary target for the development of vaccines and therapeutic interventions. The human monoclonal antibody m102.4, which targets a conserved epitope on the HeV-G receptor-binding domain, has been used under compassionate use protocols to treat individuals exposed to Hendra virus and has shown high efficacy in animal models [PMID: 21937757]. Additionally, a soluble form of the G protein (HeV-sG) serves as the basis for the Equine Hendra virus vaccine, the first vaccine licensed for use against a Biosafety Level 4 (BSL-4) agent, aimed at preventing spillover from horses to humans [PMID: 25140306].

Other names

Hendra virus G proteinHeV GAttachment glycoprotein GHenipavirus G protein

Neutralizing monoclonal antibodies such as m102.4 bind to the receptor-binding domain of the Hendra virus G protein, competitively inhibiting its interaction with the host cell receptors ephrin-B2 and ephrin-B3, thereby preventing viral attachment and subsequent membrane fusion.