{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T10:01:43Z","timestamp":1785578503810,"version":"3.56.0"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY032495"],"award-info":[{"award-number":["R01EY032495"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018719","name":"University of Missouri School of Medicine","doi-asserted-by":"publisher","award":["Research start-up funds"],"award-info":[{"award-number":["Research start-up funds"]}],"id":[{"id":"10.13039\/100018719","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015509","name":"Missouri Department of Health and Senior Services","doi-asserted-by":"publisher","award":["AOC23380006"],"award-info":[{"award-number":["AOC23380006"]}],"id":[{"id":"10.13039\/100015509","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,10,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Zika virus (ZIKV) is the lone member of Flavivirus family known to cause congenital glaucoma following\n                      <jats:italic toggle=\"yes\">in utero<\/jats:italic>\n                      exposure. The molecular mechanisms of ZIKV-induced glaucoma remain elusive, with no known therapeutic modalities. Autophagy plays a dual role in viral infections and glaucoma pathogenesis. However, how ZIKV interferes with autophagic pathways in the trabecular meshwork (TM) and whether autophagy contributes to ZIKV-induced ocular complications remains elusive. Here, we investigated the role of autophagy in ZIKV ocular pathogenesis utilizing a primary human trabecular meshwork cells (HTMC) and IFNAR1\n                      <jats:sup>-\/-<\/jats:sup>\n                      mouse model of ocular infection. Our results show that ZIKV permissively infects HTMC, elicits a dysregulated cytokine response, and triggers autophagic activity in TM and the anterior segment of the IFNAR1\n                      <jats:sup>-\/-<\/jats:sup>\n                      mouse eyes. Although ZIKV initially activates autophagy in TM, it impairs the overall autophagic flux during infection by modulating the VPS39, a HOPS complex, and STX17, a SNARE complex protein, to inhibit autophagosomal maturation. ZIKV utilizes late endosomes\/lysosomes for its replication and egress in TM. We further demonstrated that pharmacologic inhibition of autophagy at the autophagosomal-lysosomal fusion stage by hydroxychloroquine (HCQ), or bafilomycin A1 (Baf-A1), restricts viral replication in TM and ZIKV-induced ocular pathology in mice. Using RNA-seq analysis, we uncovered that autophagy modulation modulates ZIKV-altered host transcriptomes governing critical cellular pathways, including host immunity, antigen processing and presentation, and cell death. Our study is the first to demonstrate the mechanistic insight by which ZIKV manipulates autophagic activity in the ocular milieu, and precise modulation of autophagy could be a potential therapeutic avenue to treat or prevent ZIKV-induced ocular complications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">In utero<\/jats:italic>\n                      exposure to Zika virus (ZIKV) causes congenital glaucoma; however, the molecular mechanisms of ZIKV-induced glaucoma remain unknown. Here, we demonstrated that ZIKV activates the autophagic activity in the trabecular meshwork and impairs the overall autophagic flux during infection to avoid autolysosomal maturation and uses late-endosomes\/lysosomes for their egress. Inhibition of autophagy at late stages, specifically at the autophagosomal-lysosomal fusion stage, restricts viral replication and ZIKV-induced ocular complications.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01034-25","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T16:12:55Z","timestamp":1757347975000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Zika virus impairs autophagic flux in trabecular meshwork, and inhibition of autophagy restricts ocular viral transmission and associated pathology"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5401-5027","authenticated-orcid":false,"given":"Faraz","family":"Ahmad","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Ophthalmology, Mason Eye Institute, University of Missouri School of Medicine","place":["Columbia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0296-3332","authenticated-orcid":false,"given":"Prince","family":"Kumar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Ophthalmology, Mason Eye Institute, University of Missouri School of Medicine","place":["Columbia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pallav","family":"Singh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"MU Institute of Data Science and Informatics, University of Missouri","place":["Columbia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8944-4924","authenticated-orcid":false,"given":"Trupti","family":"Joshi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"MU Institute of Data Science and Informatics, University of Missouri","place":["Columbia, USA"]},{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Informatics, Biostatistics and Medical Epidemiology, University of Missouri","place":["Columbia, USA"]},{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"Christopher S Bond Life Sciences Center, University of Missouri","place":["Columbia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5517-1120","authenticated-orcid":true,"given":"Pawan Kumar","family":"Singh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Ophthalmology, Mason Eye Institute, University of Missouri School of Medicine","place":["Columbia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"WHO PAHOP. 2023. 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