Functional assessment of the glycoproteins of a novel Hendra virus variant reveals contrasting fusogenic capacities of the receptor-binding and fusion glycoproteins
HeV is a zoonotic pathogen that causes severe disease across various mammalian hosts, including horses and humans. The identification of unrecognized HeV variants, such as HeV-g2, highlights the need to investigate mechanisms that may drive their evolution, transmission, and pathogenicity. Our study reveals that HeV-g2 and HeV-g1 glycoproteins are highly conserved in identity, function, and receptor tropism, yet they differ in their abilities to induce the formation of multinucleated cells (syncytia), which is a potential marker of viral pathogenesis. By using heterotypic combinations of HeV-g2 with either HeV-g1 or NiV glycoproteins, as well as chimeric HeV-g1/HeV-g2 glycoproteins, we demonstrate that the differences in syncytial formation can be attributed to the intrinsic fusogenic capacities of each glycoprotein. Our data indicate that HeV-g2 glycoproteins have fusion phenotypes closely related to those of NiV and that fusion promotion may be a crucial factor driving the emergence of new henipaviral variants.
Authors
- Raina K. Plowright (ORCID: https://orcid.org/0000-0002-3338-6590)
- John‐Sebastian Eden (ORCID: https://orcid.org/0000-0003-1374-3551)
- C.-M. Kim
- Viraj Upadhye (ORCID: https://orcid.org/0000-0002-6755-0029)
- J. Lee (ORCID: https://orcid.org/0009-0002-4535-0269)
- David W. Buchholz (ORCID: https://orcid.org/0000-0001-8874-6648)
- Shahrzad Ezzatpour
- Alison J. Peel (ORCID: https://orcid.org/0000-0003-3538-3550)
- C Menchaca
- Z. Andrew (ORCID: https://orcid.org/0000-0002-6344-5950)
- Edward J. Annand (ORCID: https://orcid.org/0000-0002-4619-3667)
- Yao Yu Yeo (ORCID: https://orcid.org/0000-0002-7604-2296)
- Hector C. Aguilar (ORCID: https://orcid.org/0000-0001-6879-8360)
Institutions
- Griffith University (AU)
- Planetary Science Institute (US)
- Cornell University (US)
- Département Santé Animale (FR)
- Westmead Institute for Medical Research (AU)
- New York State College of Veterinary Medicine (US)
- Department of Agriculture, Fisheries and Forestry
- ACT Government (AU)
Publication Details
- Journal
- mBio
- Published
- 2024-12-20
- DOI
- https://doi.org/10.1128/mbio.03482-23
- Citations
- 3
- Primary Topic
- Virology and Viral Diseases
- Type
- article
- Field-Weighted Citation Impact
- 1.16
Funders
- National Institutes of Health
- Defense Advanced Research Projects Agency
- Advanced Research Projects Agency
- National Institute of Allergy and Infectious Diseases