{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:18:42Z","timestamp":1788585522365,"version":"build-2803163510"},"reference-count":91,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1R35GM160182"],"award-info":[{"award-number":["1R35GM160182"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["1R35GM160182"],"award-info":[{"award-number":["1R35GM160182"]}],"id":[{"id":"https:\/\/ror.org\/045p44t13","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Kaposi\u2019s sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus that causes Kaposi\u2019s sarcoma (KS), an endothelial cell-derived malignancy that primarily affects immunocompromised individuals. During lytic reactivation, KSHV expresses viral proteins that promote viral replication and modulate host signaling pathways. Here, we identified the calcium-activated chloride channel ANO1 (TMEM16A) as a previously unrecognized host factor induced by the KSHV lytic protein vGPCR. RNA sequencing, RT-qPCR, and immunofluorescence analyses demonstrated robust ANO1 upregulation in vGPCR-expressing endothelial cells and during KSHV lytic reactivation. siRNA-mediated depletion of vGPCR significantly reduced ANO1 expression, demonstrating that vGPCR contributes to ANO1 induction during infection. Functionally, ANO1 knockdown sensitized vGPCR-expressing endothelial cells to caspase-dependent apoptosis under serum-starved conditions, which was rescued by the pan-caspase inhibitor Z-VAD-FMK. In reactivated iSLK.BAC16 cells, genetic or pharmacological inhibition of ANO1 increased late apoptosis, enhanced KSHV lytic gene expression, and promoted infectious virion production. Together, these findings identify ANO1 as a vGPCR-regulated host factor that promotes cell survival and modulates KSHV lytic replication, highlighting ANO1 signaling as a potential therapeutic target in KSHV-associated disease.<\/jats:p>","DOI":"10.3390\/v18090954","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:41:18Z","timestamp":1788266478000},"page":"954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["vGPCR-Mediated ANO1 Modulation of Apoptosis Regulates Lytic KSHV Infection"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9220-3151","authenticated-orcid":false,"given":"Anisha Reddy","family":"Konakalla","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Osvaldo K.","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7254-422X","authenticated-orcid":false,"given":"Savannah E.","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9079-1090","authenticated-orcid":false,"given":"Erica L.","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1172\/JCI40567","article-title":"KSHV and the Pathogenesis of Kaposi Sarcoma: Listening to Human Biology and Medicine","volume":"120","author":"Ganem","year":"2010","journal-title":"J. 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