Structural highlights
Function
[FUS_NIPAV] Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (F protein) probably interacts with HN at the virion surface. Upon HN binding to its cellular receptor, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between cell and virion membranes. Later in infection, F proteins expressed at the plasma membrane of infected cells could mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis (By similarity).
Publication Abstract from PubMed
Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50-100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals.
An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections.,Dang HV, Chan YP, Park YJ, Snijder J, Da Silva SC, Vu B, Yan L, Feng YR, Rockx B, Geisbert TW, Mire CE, Broder CC, Veesler D Nat Struct Mol Biol. 2019 Sep 30. pii: 10.1038/s41594-019-0308-9. doi:, 10.1038/s41594-019-0308-9. PMID:31570878[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dang HV, Chan YP, Park YJ, Snijder J, Da Silva SC, Vu B, Yan L, Feng YR, Rockx B, Geisbert TW, Mire CE, Broder CC, Veesler D. An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections. Nat Struct Mol Biol. 2019 Sep 30. pii: 10.1038/s41594-019-0308-9. doi:, 10.1038/s41594-019-0308-9. PMID:31570878 doi:http://dx.doi.org/10.1038/s41594-019-0308-9
