Liu Tiezhu, Wang Xueqi, Fang Yang, Zhang Ping, Sun Qiang, Li Jiandong, Wang Shiwen
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.
Department of General Surgery, Capital Center for Children's Health, Capital Medical University, Beijing 100020, China.
Pathogens. 2025 Jul 9;14(7):677. doi: 10.3390/pathogens14070677.
SNX11, a sorting nexin protein localized on the endosomal membrane, is an important protein closely related to protein sorting and endosomal trafficking. Previously, through a genome-wide CRISPR screening, we identified SNX11 as a critical protein for the entry of Dabie bandavirus. SNX11 deletion significantly inhibits the replication of Dabie bandavirus. We further discovered that the loss of SNX11 alters endosomal pH, potentially affecting the release process of Dabie bandavirus from endosomes to the cytoplasm. However, the mechanism by which SNX11 modulates endosomal pH and whether SNX11 deletion similarly inhibits other viruses remain to be elucidated. This study reveals that SNX11 can interact with the V1 subunit of the endosomal proton pump V-ATPase, affecting the expression level of this subunit on the endosomal membrane and thereby disrupting the assembly of V-ATPase. Additionally, we found that SNX11 deletion significantly inhibits the replication of dengue virus, hantavirus, and influenza virus. These findings suggest that SNX11 may be a key protein in the process of viral infection and could serve as a broad-spectrum antiviral target.
分选连接蛋白11（SNX11）是一种定位于内体膜的分选连接蛋白，是一种与蛋白质分选和内体运输密切相关的重要蛋白质。此前，通过全基因组CRISPR筛选，我们确定SNX11是大别山带状病毒进入细胞的关键蛋白。缺失SNX11会显著抑制大别山带状病毒的复制。我们进一步发现，SNX11的缺失会改变内体pH值，可能影响大别山带状病毒从内体释放到细胞质的过程。然而，SNX11调节内体pH值的机制以及SNX11的缺失是否同样抑制其他病毒仍有待阐明。本研究表明，SNX11可与内体质子泵V-ATPase的V1亚基相互作用，影响该亚基在内体膜上的表达水平，从而破坏V-ATPase的组装。此外，我们发现缺失SNX11会显著抑制登革病毒、汉坦病毒和流感病毒的复制。这些发现表明，SNX11可能是病毒感染过程中的关键蛋白，并可作为广谱抗病毒靶点。
