2. Academic Validation
  3. Molecular characterization of Ebola virus glycoprotein V75A substitution in the 2018-2020 epidemic

Molecular characterization of Ebola virus glycoprotein V75A substitution in the 2018-2020 epidemic

  • Cell. 2026 Feb 5;189(3):818-831.e19. doi: 10.1016/j.cell.2025.12.022.
Linjin Fan 1,  Yulong Wang 2,  Yinghao Wang 3,  Zequn Wang 3,  Xiaofeng Yang 3,  Chudan Liang 3,  Chongguang Yang 4,  Nan Liu 5,  Jun Zheng 6,  Weifang Kang 3,  Pengfei Ye 3,  Pei Sun 6,  Wendi Shi 3,  Xinyi Guo 4,  Weijian Wu 3,  Jian-Rong Yang 7,  Quan Liu 8,  Linna Liu 9,  Jun Qian 10
Affiliations

Affiliations

  • 1 School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China; Shenzhen Key Laboratory of Pathogenic Microbes and Biosafety, Shenzhen 518107, China; Guangdong Provincial Highly Pathogenic Microorganism Science Data Centre, Guangzhou 510030, China.
  • 2 Guangzhou Key Laboratory of Clinical Pathogen Research for Emerging and Major Infectious Diseases, Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510440, China; Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510030, China.
  • 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510030, China.
  • 4 School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China; Shenzhen Key Laboratory of Pathogenic Microbes and Biosafety, Shenzhen 518107, China.
  • 5 Department of Infectious Diseases, Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun 130031, China.
  • 6 Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou 510275, China.
  • 7 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510030, China. Electronic address: [email protected].
  • 8 Department of Infectious Diseases, Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun 130031, China; Chinese Medicine Guangdong Laboratory, State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical College, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510405, China; School of Medicine, Shihezi University, Shihezi 832003, China. Electronic address: [email protected].
  • 9 Guangzhou Key Laboratory of Clinical Pathogen Research for Emerging and Major Infectious Diseases, Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510440, China. Electronic address: [email protected].
  • 10 School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China; Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510030, China; Shenzhen Key Laboratory of Pathogenic Microbes and Biosafety, Shenzhen 518107, China; Guangdong Provincial Highly Pathogenic Microorganism Science Data Centre, Guangzhou 510030, China. Electronic address: [email protected].
PMID: 41576953 DOI: 10.1016/j.cell.2025.12.022
Abstract

The 2018-2020 Ebola virus disease (EVD) epidemic facilitated the emergence of viral mutations, enhancing the potential for host adaptation during sustained human transmission. Here, we identified the Ebola virus (EBOV) glycoprotein V75A (GP-V75A) substitution as a dominant variant during the epidemic. This substitution, located within the receptor-binding domain, emerged early in the outbreak and rapidly reached high prevalence. GP-V75A demonstrated enhanced infectivity in multiple cell lines and murine models. Mechanistically, GP-V75A increased viral GP binding affinity to the host receptor Niemann-Pick C1 (NPC1) and reduced the dependency on endosomal cysteine proteases for entry. Notably, GP-V75A also significantly reduced the efficacy of NPC1-targeting compounds and neutralizing antibodies. Epidemiological analysis indicated that the rise in GP-V75A prevalence coincided with the increase in case number during the outbreak. These findings provide crucial insights into the evolutionary adaptation of EBOV during large-scale outbreaks and underscore the importance of real-time genomic surveillance for improving epidemic preparedness.

Keywords

Ebola virus; GP-V75A; binding affinity; genomic epidemiology; glycoprotein; infectivity.

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