{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:49:08Z","timestamp":1791161348334,"version":"4.1.0"},"reference-count":84,"publisher":"American Society for Microbiology","issue":"24","license":[{"start":{"date-parts":[[2014,12,15]],"date-time":"2014-12-15T00:00:00Z","timestamp":1418601600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2014,12,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The cGAS\/STING DNA sensing complex has recently been established as a predominant pathogen recognition receptor (PRR) for DNA-directed type I interferon (IFN) innate immune activation. Using replication-defective adenovirus vectors and replication-competent wild-type adenovirus, we have modeled the influence of the cGAS\/STING cascade in permissive human cell lines (A549, HeLa, ARPE19, and THP1). Wild-type adenovirus induced efficient early activation of the cGAS\/STING cascade in a cell-specific manner. In all responsive cell lines, cGAS\/STING short hairpin RNA (shRNA) knockdown resulted in a loss of TBK1 and interferon response factor 3 (IRF3) activation, a lack of beta interferon transcript induction, loss of interferon-dependent STAT1 activation, and diminished induction of interferon-stimulated genes (ISGs). Adenoviruses that infect through the coxsackievirus-adenovirus receptor (CAR) (Ad2 and Ad5) and the CD46 (Ad35) and desmoglein-2 (Ad7) viral receptors all induce the cGAS\/STING\/TBK1\/IRF3 cascade. The magnitude of the IRF3\/IFN\/ISG antiviral response was strongly influenced by serotype, with Ad35&gt;Ad7&gt;Ad2. For each serotype, no enhancement of viral DNA replication or virus production occurred in cGAS or STING shRNA-targeted cell line pools. We found no replication advantage in permissive cell lines that do not trigger the cGAS\/STING cascade following infection. The cGAS\/STING\/TBK1\/IRF3 cascade was not a direct target of viral antihost strategies, and we found no evidence that Ad stimulation of the cGAS\/STING DNA response had an impact on viral replication efficiency.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>This study shows for the first time that the cGAS DNA sensor directs a dominant IRF3\/IFN\/ISG antiviral response to adenovirus in human cell lines. Activation of cGAS occurs with viruses that infect through different high-affinity receptors (CAR, CD46, and desmoglein-2), and the magnitude of the cGAS\/STING DNA response cascade is influenced by serotype-specific functions. Furthermore, activation of the cGAS cascade occurred in a cell-specific manner. Activation of the cGAS\/STING response did not impact viral replication, and viral immune evasion strategies did not target the cGAS\/STING\/TBK1\/IRF3 cascade. These studies provide novel insight into the early innate recognition response to adenovirus.<\/jats:p>","DOI":"10.1128\/jvi.02608-14","type":"journal-article","created":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T07:04:38Z","timestamp":1412838278000},"page":"14426-14439","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["Unabated Adenovirus Replication following Activation of the cGAS\/STING-Dependent Antiviral Response in Human Cells"],"prefix":"10.1128","volume":"88","author":[{"given":"Eric","family":"Lam","sequence":"first","affiliation":[{"name":"Weill Medical College of Cornell University, Department of Microbiology and Immunology, Molecular Biology Graduate Program, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Falck-Pedersen","sequence":"additional","affiliation":[{"name":"Weill Medical College of Cornell University, Department of Microbiology and Immunology, Molecular Biology Graduate Program, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1283287"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1309\/AWXDGNC5D70EN7YT"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/176418"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.18.9814"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/10430349950018364"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.211423598"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.4.2004-2015.1995"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.10.7209-7212.1996"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1515\/znb-1967-0211"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01240504"},{"key":"e_1_3_2_12_2","first-page":"337","article-title":"Different interferon-inducing ability of human adenovirus types in chick embryo cells","volume":"27","author":"Toth M","year":"1983","unstructured":"TothMBakayMTarodiBTothSPusztaiRBeladiI. 1983. 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