{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T01:58:25Z","timestamp":1772589505859,"version":"3.50.1"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370172"],"award-info":[{"award-number":["32370172"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022973","name":"Guangzhou Institute of Respiratory Health","doi-asserted-by":"crossref","award":["SRPG22-002"],"award-info":[{"award-number":["SRPG22-002"]}],"id":[{"id":"10.13039\/100022973","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,5,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>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.<\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>Virus 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.<\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/jvi.00002-25","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T13:00:13Z","timestamp":1745586013000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Syntaxin-6 restricts SARS-CoV-2 infection by facilitating virus trafficking to autophagosomes"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3248-1710","authenticated-orcid":false,"given":"Hao","family":"Sun","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences","place":["Wuhan, China"]},{"name":"University of Chinese Academy of 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