2026-01-23 中山大学(SYSU)
A schematic diagram illustrating how the GP-V75A mutation enhances the infectivity of the Ebola virus.
<関連情報>
- https://www.sysu.edu.cn/sysuen/info/1012/58411.htm
- https://www.cell.com/cell/fulltext/S0092-8674(25)01435-7
2018～2020年の流行におけるエボラウイルス糖タンパク質V75A変異の分子的特徴 Molecular characterization of Ebola virus glycoprotein V75A substitution in the 2018–2020 epidemic
Linjin Fan ∙ Yulong Wang ∙ Yinghao Wang ∙ … ∙ Quan Liu ∙ Linna Liu ∙ Jun Qian
Cell Published:January 22, 2026
DOI:https://doi.org/10.1016/j.cell.2025.12.022
Highlights
- Ebola virus GP-V75A substitution emerged early and dominated the epidemic
- V75A increases viral infectivity in multiple cell lines and murine models
- V75A enhances viral receptor binding affinity and reduces cysteine protease dependence
- V75A reduces efficacy of compound-targeting NPC1 loop 2
Summary
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.
