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TitleStructure and antigenicity of divergent Henipavirus fusion glycoproteins.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 3577, Year 2023
Publish dateJun 16, 2023
AuthorsAriel Isaacs / Yu Shang Low / Kyle L Macauslane / Joy Seitanidou / Cassandra L Pegg / Stacey T M Cheung / Benjamin Liang / Connor A P Scott / Michael J Landsberg / Benjamin L Schulz / Keith J Chappell / Naphak Modhiran / Daniel Watterson /
PubMed AbstractIn August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This virus is closely related to Mòjiāng virus (MojV), and ...In August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This virus is closely related to Mòjiāng virus (MojV), and both are divergent from the bat-borne HNV members, Nipah (NiV) and Hendra (HeV) viruses. The spillover of LayV is the first instance of a HNV zoonosis to humans outside of NiV and HeV, highlighting the continuing threat this genus poses to human health. In this work, we determine the prefusion structures of MojV and LayV F proteins via cryogenic electron microscopy to 2.66 and 3.37 Å, respectively. We show that despite sequence divergence from NiV, the F proteins adopt an overall similar structure but are antigenically distinct as they do not react to known antibodies or sera. Glycoproteomic analysis revealed that while LayV F is less glycosylated than NiV F, it contains a glycan that shields a site of vulnerability previously identified for NiV. These findings explain the distinct antigenic profile of LayV and MojV F, despite the extent to which they are otherwise structurally similar to NiV. Our results carry implications for broad-spectrum HNV vaccines and therapeutics, and indicate an antigenic, yet not structural, divergence from prototypical HNVs.
External linksNat Commun / PubMed:37328468 / PubMed Central
MethodsEM (single particle)
Resolution2.66 - 3.37 Å
Structure data

EMDB-29299, PDB-8fmx:
Langya virus F glycoprotein ectodomain in prefusion form
Method: EM (single particle) / Resolution: 3.37 Å

EMDB-29300, PDB-8fmy:
Mojiang virus F ectodomain in prefusion form
Method: EM (single particle) / Resolution: 2.66 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • langya virus
  • mojiang virus
KeywordsVIRAL PROTEIN / F ectodomain / prefusion

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