A structural basis for antibody-mediated neutralization of Nipah virus reveals a site of vulnerability at the fusion glycoprotein apex

Victoria A. Avanzato, Kasopefoluwa Y. Oguntuyo, Marina Escalera-Zamudio, Bernardo Gutierrez, Michael Golden, Sergei L. Kosakovsky Pond, Rhys Pryce, Thomas S. Walter, Jeffrey Seow, Katie J. Doores, Oliver G. Pybus, Vincent J. Munster, Benhur Lee, Thomas A. Bowden

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes frequent outbreaks of severe neurologic and respiratory disease in humans with high case fatality rates. The 2 glycoproteins displayed on the surface of the virus, NiV-G and NiV-F, mediate host-cell attachment and membrane fusion, respectively, and are targets of the host antibody response. Here, we provide a molecular basis for neutralization of NiV through antibody-mediated targeting of NiV-F. Structural characterization of a neutralizing antibody (nAb) in complex with trimeric prefusion NiV-F reveals an epitope at the membrane-distal domain III (DIII) of the molecule, a region that undergoes substantial refolding during host-cell entry. The epitope of this monoclonal antibody (mAb66) is primarily protein-specific and we observe that glycosylation at the periphery of the interface likely does not inhibit mAb66 binding to NiV-F. Further characterization reveals that a Hendra virus-F–specific nAb (mAb36) and many antibodies in an antihenipavirus-F polyclonal antibody mixture (pAb835) also target this region of the molecule. Integrated with previously reported paramyxovirus F−nAb structures, these data support a model whereby the membrane-distal region of the F protein is targeted by the antibody-mediated immune response across henipaviruses. Notably, our domain-specific sequence analysis reveals no evidence of selective pressure at this region of the molecule, suggestive that functional constraints prevent immune-driven sequence variation. Combined, our data reveal the membrane-distal region of NiV-F as a site of vulnerability on the NiV surface.

Original languageEnglish
Pages (from-to)25057-25067
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number50
StatePublished - 10 Dec 2019


  • Antibody response
  • Glycoprotein
  • Henipavirus
  • Structure
  • Viral fusion


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