{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:59:02Z","timestamp":1791953942201,"version":"4.3.4"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Although guanine nucleotide-binding protein (G protein)\u2013coupled receptors (GPCRs) constitute the largest cell surface membrane receptor family and transduce thousands of extracellular signals into the cytoplasm, only four kinds of G protein \u03b1 subunits (G\u03b1s, G\u03b1i\/o, G\u03b1q\/11, and G\u03b112\/13) are coupled to regulate cAMP or phosphatidylinositol signals. Growing evidence suggests that viruses tend to hijack GPCRs and harness their activated intracellular signaling pathways. Thus, understanding the roles of G protein signaling will further uncover the GPCR signaling pathways that are exploited by viruses. In this study, we demonstrate that the expression of GNAQ (Gq \u03b1 subunit) was downregulated during viral infection and that small interfering RNA\u2013mediated GNAQ knockdown protected host cells from both vesicular stomatitis virus (VSV) and HSV type 1 infection. Meanwhile, VSV and HSV type 1 replication was reduced significantly in Gnaq-deficient macrophages. Accordingly, the VSV distribution in the liver, spleen, and lung was reduced in Gnaq-deficient mice during VSV infection, and Gnaq-deficient mice were much more resistant to VSV infection than wild-type mice. Mechanistically, GNAQ limits type I IFN production through the canonical PLC-\u03b2\/Ca2+\/CALNA signaling pathway, which has been demonstrated to dephosphorylate virus-activated TANK-binding kinase 1 (TBK1). Thus, our data demonstrate that GNAQ negatively regulates the antiviral innate immune responses in a calcineurin-dependent manner. These findings also provide insights into the function and cross-talk of the classic GPCR signaling pathway with antiviral innate immune responses and suggest a potential therapeutic role for GNAQ in controlling viral diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1900427","type":"journal-article","created":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T20:44:06Z","timestamp":1563569046000},"page":"1288-1297","source":"Crossref","is-referenced-by-count":10,"title":["GNAQ Negatively Regulates Antiviral Innate Immune Responses in a Calcineurin-Dependent Manner"],"prefix":"10.1093","volume":"203","author":[{"given":"Ning","family":"Wang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjun","family":"Huang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Xiong","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naiyang","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanxi","family":"Xi","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilun","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyao","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Qian","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology, Shanghai Fengxian Central Hospital , Shanghai 201400 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5402-6527","authenticated-orcid":false,"given":"Bing","family":"Du","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,9,1]]},"reference":[{"key":"2025030417541752300_r1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nri3787","article-title":"Type I interferons in infectious disease","volume":"15","author":"McNab","year":"2015","journal-title":"Nat. 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