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TitleCryo-EM structures of Měnglà virus GP reveal combined Ebola- and Marburg-like epitope masking strategies for antibody evasion.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 123, Issue 23, Page e2529436123, Year 2026
Publish dateJun 9, 2026
AuthorsLongyu Wang / Binqian Zou / Banghui Liu / Yong Ma / Lu Xue / Gul Habib / Xinglou Yang / Xinwen Chen / Jiantao Chen / Jincun Zhao / Ying Zhang / Zifeng Yang / Jun He / Xiaoli Xiong /
PubMed AbstractEbola virus (EBOV) and Marburg virus (MARV) are highly lethal filoviruses that cause severe hemorrhagic fever in humans. A recently identified bat-borne filovirus, Měnglà virus (MLAV), uses the ...Ebola virus (EBOV) and Marburg virus (MARV) are highly lethal filoviruses that cause severe hemorrhagic fever in humans. A recently identified bat-borne filovirus, Měnglà virus (MLAV), uses the same NPC1 receptor as EBOV and MARV, raising concerns about its potential cross-species transmission. Here, we report cryo-EM structures of the MLAV surface glycoprotein (GP) in its unbound form and in complex with the MARV-neutralizing antibody MR191. MLAV GP exhibits distinctive structural features in the Wing and heptad repeat 1D (HR1D) regions, retains a visible Cap structure even after protease treatment, and contains a MARV GP-like α2 helix. MR191, a broadly neutralizing marburgvirus antibody that targets the conserved NPC1 receptor-binding pocket in MLAV GP, nonetheless exhibits impaired neutralizing activity, likely due to shielding by the MLAV Cap. In addition, the MLAV mucin-like domain, α2 helix, and HR1A region hinder binding by representative broadly neutralizing ebolavirus antibodies targeting the GP-waist, including 6D6, CA45, ADI-15878, and ADI-15946. Together, these results provide the first structural insights into MLAV GP and identify immune evasion driven by structural and sequence divergence as a major challenge for pan-filovirus antibody development.
External linksProc Natl Acad Sci U S A / PubMed:42247561 / PubMed Central
MethodsEM (single particle)
Resolution3.08 - 3.47 Å
Structure data

66501

9x3j

EMDB-66501, PDB-9x3j:
Glycoprotein of Mengla Virus with MR191 Fab bound
Method: EM (single particle) / Resolution: 3.47 Å

66502

9x3k

EMDB-66502, PDB-9x3k:
apo state of Mengla Virus Glycoprotein
Method: EM (single particle) / Resolution: 3.08 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • dianlovirus menglaense
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / Mengla Virus Glycoprotein

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