tetano
Editor, Senior Moderator
J Virol
. 2025 Apr 25:e0000225.
doi: 10.1128/jvi.00002-25. Online ahead of print. Syntaxin-6 restricts SARS-CoV-2 infection by facilitating virus trafficking to autophagosomes
Hao Sun[SUP] 1 2 [/SUP], Qi Yang[SUP] 3 [/SUP], Yecheng Zhang[SUP] 1 4 [/SUP], Saisai Cui[SUP] 1 2 [/SUP], Zhe Zhou[SUP] 1 [/SUP], Peilu Zhang[SUP] 1 2 [/SUP], Lijia Jia[SUP] 1 [/SUP], Mingxia Zhang[SUP] 1 [/SUP], Yun Wang[SUP] 1 [/SUP], Xinwen Chen[SUP] 1 3 [/SUP], Rongjuan Pei[SUP] 1 [/SUP]
Affiliations
Despite the diminishing global impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus continues to circulate and undergo mutations, posing ongoing challenges for public health. A comprehensive understanding of virus entry mechanisms is crucial for managing new epidemic strains. However, the cellular processes post-endocytosis remain largely unexplored. This study employs proximity labeling to examine proteins near ACE2 post-viral infection and identified syntaxin-6 (STX6) as a factor that inhibits SARS-CoV-2 infection by impeding the endocytic release of the virus. SARS-CoV-2 infection enhances early endosome recruitment of STX6. STX6 appears to hinder the maturation of viral particles-laden early endosomes into late endosomes, from which the virus could escape. Instead, it promotes the trafficking of the virus toward the autophagy-lysosomal degradation pathway. STX6 exhibits a broad-spectrum effect against various SARS-CoV-2 variants and several other viruses that enter via endocytosis. We report for the first time the function of STX6 as a restrictive factor in viral infection.IMPORTANCEVirus entry is the first step of the virus life cycle, and the exploitation of the endo-lysosome pathway for cellular entry by viruses has been well documented. Meanwhile, the intrinsic defense present within cells interferes with virus entry. We identified STX6 as a host restriction factor for viral entry by facilitating the virus trafficking to the autophagy-lysosomal degradation pathway. Notably, STX6 exhibits broad-spectrum antiviral activity against diverse severe acute respiratory syndrome coronavirus 2 variants and other viruses employing endocytosis for entry.
Keywords: SARS-CoV-2; SNARE; autophagy; syntaxin-6; virus entry.
. 2025 Apr 25:e0000225.
doi: 10.1128/jvi.00002-25. Online ahead of print. Syntaxin-6 restricts SARS-CoV-2 infection by facilitating virus trafficking to autophagosomes
Hao Sun[SUP] 1 2 [/SUP], Qi Yang[SUP] 3 [/SUP], Yecheng Zhang[SUP] 1 4 [/SUP], Saisai Cui[SUP] 1 2 [/SUP], Zhe Zhou[SUP] 1 [/SUP], Peilu Zhang[SUP] 1 2 [/SUP], Lijia Jia[SUP] 1 [/SUP], Mingxia Zhang[SUP] 1 [/SUP], Yun Wang[SUP] 1 [/SUP], Xinwen Chen[SUP] 1 3 [/SUP], Rongjuan Pei[SUP] 1 [/SUP]
Affiliations
- PMID: 40277356
- DOI: 10.1128/jvi.00002-25
Despite the diminishing global impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus continues to circulate and undergo mutations, posing ongoing challenges for public health. A comprehensive understanding of virus entry mechanisms is crucial for managing new epidemic strains. However, the cellular processes post-endocytosis remain largely unexplored. This study employs proximity labeling to examine proteins near ACE2 post-viral infection and identified syntaxin-6 (STX6) as a factor that inhibits SARS-CoV-2 infection by impeding the endocytic release of the virus. SARS-CoV-2 infection enhances early endosome recruitment of STX6. STX6 appears to hinder the maturation of viral particles-laden early endosomes into late endosomes, from which the virus could escape. Instead, it promotes the trafficking of the virus toward the autophagy-lysosomal degradation pathway. STX6 exhibits a broad-spectrum effect against various SARS-CoV-2 variants and several other viruses that enter via endocytosis. We report for the first time the function of STX6 as a restrictive factor in viral infection.IMPORTANCEVirus entry is the first step of the virus life cycle, and the exploitation of the endo-lysosome pathway for cellular entry by viruses has been well documented. Meanwhile, the intrinsic defense present within cells interferes with virus entry. We identified STX6 as a host restriction factor for viral entry by facilitating the virus trafficking to the autophagy-lysosomal degradation pathway. Notably, STX6 exhibits broad-spectrum antiviral activity against diverse severe acute respiratory syndrome coronavirus 2 variants and other viruses employing endocytosis for entry.
Keywords: SARS-CoV-2; SNARE; autophagy; syntaxin-6; virus entry.