{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:44:33Z","timestamp":1790707473114,"version":"4.1.0"},"reference-count":63,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"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":["32000128, 82460013"],"award-info":[{"award-number":["32000128, 82460013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007471","name":"Applied Basic Research Foundation of Yunnan Province","doi-asserted-by":"publisher","award":["202501AS070010"],"award-info":[{"award-number":["202501AS070010"]}],"id":[{"id":"10.13039\/100007471","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018576","name":"Ten Thousand Talent Plans for Young Top-notch Talents of Yunnan Province","doi-asserted-by":"publisher","award":["XDYCQNRC-2022-0300"],"award-info":[{"award-number":["XDYCQNRC-2022-0300"]}],"id":[{"id":"10.13039\/501100018576","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yunnan health training project of high level talents"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,12,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      We aimed to demonstrate whether coxsackievirus A10 (CV-A10) perturbed the fusion between autophagosomes and lysosomes to cause viral nonlytic spread and inflammatory cytokine release at the blood-brain barrier (BBB), thereby contributing to neuropathological damage. CV-A10-induced autophagic secretory pathway at the cellular level was examined using western blot, immunofluorescence, and flow cytometry methods. Then, the mechanism of autophagic secretory pathway in the neuropathogenesis of CV-A10 infection was demonstrated by constructing a suckling mouse model and combining behavioral, pathological, and molecular biological methods. The expression levels of autophagic secretory pathway-related proteins, extracellular inflammatory cytokines, and viral particles were significantly increased during CV-A10 infection. Moreover, 3-methyladenine significantly impeded the levels of autophagic secretory pathway-related proteins and the release of inflammatory cytokines or viruses; GW4869 and chloroquine partially suppressed these changes, whereas bafilomycin A1 had no obvious effects on these changes, implying that the autophagic secretory pathway without endosome or lysosome involvement might represent a new mode of inflammatory cytokine release and virus spread from intracellular to extracellular environments. Finally, an\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      suckling mouse model further found that treatment with GW4869 significantly relieved the clinical symptoms and mortality of CV-A16-infected mice and inhibited the spread of the virus and the release of inflammatory cytokines. Our findings provide the first evidence that CV-A10 might trigger the autophagic secretory pathway by limiting autophagosome-lysosome fusion to complete the transmembrane nonlytic transmission of the virus at the BBB and the secretion of inflammatory cytokines, ultimately accelerating neuropathological damage.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>This study provided the first evidence that coxsackievirus A10 (CV-A10) might use the autophagic secretory pathway for nonlytic intercellular release to complete transmembrane transmission at the blood-brain barrier and inflammatory cytokine secretion to accelerate the formation of neuroinflammation in infected hosts, which not only gave us a new understanding of the neuropathogenesis caused by CV-A10 but also offered a promising target to develop CV-A10 antiviral drugs.<\/jats:p>\n                    <\/jats:sec>\n             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