Structure and design of Langya virus glycoprotein antigens.

Autor:	Wang Z; Department of Biochemistry, University of Washington, Seattle, WA 98195., McCallum M; Department of Biochemistry, University of Washington, Seattle, WA 98195., Yan L; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD 20814., Gibson CA; Department of Biochemistry, University of Washington, Seattle, WA 98195., Sharkey W; Department of Biochemistry, University of Washington, Seattle, WA 98195., Park YJ; Department of Biochemistry, University of Washington, Seattle, WA 98195.; HHMI, Seattle, WA 98195., Dang HV; Department of Biochemistry, University of Washington, Seattle, WA 98195., Amaya M; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD 20814., Person A; Department of Biochemistry, University of Washington, Seattle, WA 98195., Broder CC; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD 20814., Veesler D; Department of Biochemistry, University of Washington, Seattle, WA 98195.; HHMI, Seattle, WA 98195.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Apr 16; Vol. 121 (16), pp. e2314990121. Date of Electronic Publication: 2024 Apr 09.
DOI:	10.1073/pnas.2314990121
Abstrakt:	Langya virus (LayV) is a recently discovered henipavirus (HNV), isolated from febrile patients in China. HNV entry into host cells is mediated by the attachment (G) and fusion (F) glycoproteins which are the main targets of neutralizing antibodies. We show here that the LayV F and G glycoproteins promote membrane fusion with human, mouse, and hamster target cells using a different, yet unknown, receptor than Nipah virus (NiV) and Hendra virus (HeV) and that NiV- and HeV-elicited monoclonal and polyclonal antibodies do not cross-react with LayV F and G. We determined cryoelectron microscopy structures of LayV F, in the prefusion and postfusion states, and of LayV G, revealing their conformational landscape and distinct antigenicity relative to NiV and HeV. We computationally designed stabilized LayV G constructs and demonstrate the generalizability of an HNV F prefusion-stabilization strategy. Our data will support the development of vaccines and therapeutics against LayV and closely related HNVs. Competing Interests: Competing interests statement:M.M. and D.V. are inventors on patent applications submitted by the University of Washington related to LayV G stabilization. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Databáze:	MEDLINE
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