{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:50:42Z","timestamp":1792612242660,"version":"4.5.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"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":[[2025,11,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>All viruses that establish successful infections express proteins that\n                        inhibit innate anti-viral pathways such as the stimulator of interferon\n                        genes (STING) pathway. In response, cells have evolved mechanisms to limit\n                        viruses by modifying these viral proteins via post-translational\n                        modifications (PTMs). One potent PTM, protein-S-nitrosylation, inhibits the\n                        ability of human cytomegalovirus (HCMV) to undermine the establishment of an\n                        anti-viral state. The direct nitrosylation of HCMV tegument protein pp71 at\n                        a central cysteine within its pRB binding domain reduces pp71\u2019s\n                        ability to limit the activity of STING. Two different proteins encoded by\n                        unrelated DNA viruses, adenovirus (AdV) E1A and human papillomavirus (HPV)\n                        E7, also contain a pRB binding domain and inhibit STING like pp71. Herein,\n                        we report that E1A and E7 are both protein-S-nitrosylated like pp71. Stable\n                        cell lines expressing a WT, or mutants in which the predicted modified\n                        cysteine was changed to the closely related serine amino acid, thus blocking\n                        protein-S-nitrosylation, revealed that E1A and E7 are both\n                        protein-S-nitrosylated. Furthermore, induction of the STING pathway promoted\n                        IFN-\u03b21 transcript production and the phosphorylation of IRF3, which\n                        was limited in E1A and E7 stable cell lines. Mutant stable cell lines\n                        exhibited a stronger inhibition of IFN-\u03b21 transcription and reduced\n                        IRF3 phosphorylation, suggesting that the PTM limits WT viral protein\n                        inhibition of STING. Furthermore, both E1a and E7 can complement the\n                        replication of a HCMV that lacks pp71 during times of STING activation.\n                        These observations support a model in which protein-S-nitrosylation of viral\n                        virulence factors may function as an anti-viral mechanism in DNA virus\n                        infections.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>DNA viruses, such as HCMV, AdV, and HPV, have the capacity to cause\n                            significant disease. Infection with AdV can cause severe lower\n                            respiratory and liver disease in children, and HPV infection is\n                            persistent and is a causative agent of cancer. Thus, these infections\n                            can be a severe health risk. Host cells have adapted innate responses\n                            like protein S-nitrosylation to limit viral replication. Our previous\n                            work reported that direct nitrosylation of two HCMV viral proteins, pp65\n                            and pp71, limits their ability to undermine host anti-viral responses.\n                            Herein, we investigated whether protein-S-nitrosylation of AdV and HPV\n                            proteins inhibits their functions, suggesting that this PTM is an\n                            anti-viral mechanism. This may provide insight into the development of\n                            broad anti-viral therapeutics for persistent viral infections.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01456-25","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:03:10Z","timestamp":1760360590000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Protein-S-nitrosylation of adenovirus-5 E1A and human papillomavirus                    16 E7 limits their ability to inhibit STING activity"],"prefix":"10.1128","volume":"99","author":[{"given":"Justin B.","family":"Cox","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/040kfrw16","id-type":"ROR","asserted-by":"publisher"}],"name":"Microbiology and Immunology Department, SUNY-Upstate Medical University","place":["Syracuse, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3449-5024","authenticated-orcid":true,"given":"Eain A.","family":"Murphy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/040kfrw16","id-type":"ROR","asserted-by":"publisher"}],"name":"Microbiology and Immunology Department, SUNY-Upstate Medical University","place":["Syracuse, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.5.3.262"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00116-13"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v10.i35.12837"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-35761-6.00010-9"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jobcr.2017.08.003"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0602-7"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.1291"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034509333371"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07317"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900850106"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.09.003"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00640-08"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.05.009"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12306"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02702-13"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13348"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02483-16"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab3291"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28310"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.11.8.4253-4265.1991"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1590607"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2537532"},{"key":"e_1_3_4_24_2","first-page":"4620","article-title":"E7 protein of human papilloma virus-16\n                        induces degradation of retinoblastoma protein through the\n                        ubiquitin-proteasome pathway","volume":"56","author":"Boyer SN","year":"1996","unstructured":"Boyer SN, Wazer DE, Band V. 1996. 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