OmniVira

Cryo-EM structures of Měnglà virus GP reveal combined Ebola- and Marburg-like epitope masking strategies for antibody evasion.

Longyu Wang1,2,3 Binqian Zou3,4 Banghui Liu3 Yong Ma3 Lu Xue3 Gul Habib3 Xinglou Yang5 Xinwen Chen2 Jiantao Chen4 Jincun Zhao2,4,6 Ying Zhang7 Zifeng Yang2,4 Jun He1,3 Xiaoli Xiong1,2,3
Affiliations 7 institutions
  1. Guangzhou Medical University-Guangzhou Institutes of Biomedicine and Health Joint School of Life Sciences, Guangdong Provincial Key Laboratory of Protein Modification and Disease, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.
  2. Guangzhou National Laboratory, Guangzhou, Guangdong 510005, China.
  3. State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China.
  4. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China.
  5. Key Laboratory of Genetic Evolution and Animal Models, Yunnan International Joint Laboratory of Zoonotic Viruses, Yunnan Key Laboratory of Biodiversity Information, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
  6. Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
  7. Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, China.
PMID42247561 DOI10.1073/pnas.2529436123 Year2026 Journal Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A Languageeng Statusppublish

Abstract

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.

Supporting text Virus Host Location
antibody evasion 1 cryo-EM structure 9 filovirus glycoprotein 1 Měnglà virus 0

Evidence records

2 total
Functional Mechanism
2 records · 2 evidence types
Evidence type Receptor Usage
1 records
OVE11270 Receptor Usage
Key finding

Měnglà virus glycoprotein uses the same NPC1 receptor as Ebola virus and Marburg virus for host-cell entry.

Virus
Měnglà virus
Host
Not specified
Location
Not specified
Supporting text

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.

Method
structural analysis | cryo-EM
Receptors
NPC1 receptor
Evidence type Molecular Adaptation
1 records
OVE11271 Molecular Adaptation
Key finding

Cryo-EM structural analysis shows that the Měnglà virus glycoprotein possesses distinct Cap, mucin-like, α2 helix, and HR1 region features that mediate antibody escape through epitope masking.

Virus
Měnglà virus
Host
Not specified
Location
Not specified
Supporting text

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.

Genes or proteins
GP | glycoprotein | mucin-like domain | α2 helix | HR1 region | Cap region
Receptors
NPC1
Host factors
MR191
Mechanism types
immune escape | receptor binding