{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:12:58Z","timestamp":1789150378221,"version":"build-2803163510"},"reference-count":48,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"37","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI184716"],"award-info":[{"award-number":["AI184716"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA285192"],"award-info":[{"award-number":["CA285192"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG070904"],"award-info":[{"award-number":["AG070904"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG088625"],"award-info":[{"award-number":["AG088625"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,9,11]]},"abstract":"<jats:p>\n                    Herpesviruses are common pathogens of the oral cavity, yet how they interact with other oral microbes are poorly understood. Using murine gamma-herpesvirus 68 (MHV68) as a model for human gamma-herpesviruses, we find that ISGylation is hijacked to facilitate viral capsid assembly and lytic replication. Coinfection with the oral\n                    <jats:italic toggle=\"yes\">Aggregatibacter actinomycetemcomitans<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">A.actinomycetemcomitans<\/jats:italic>\n                    ) and MHV68 synergistically induced interferon-stimulated gene 15 (ISG15) expression and global ISGylation. Proteomic profiling revealed viral structural proteins as the dominant targets of ISGylation in MHV68-infected cells. Genetic ablation of ISGylation, using ISGylation-resistant recombinant MHV68 and ISG15-deficient mouse embryonic fibroblasts (MEFs), demonstrated that ISGylation of the major capsid protein ORF25 is required for efficient capsid assembly and maturation into the infectious C-type virions. Notably, introduction of a de novo ISGylation site into the ISGylation-resistant MHV68 was sufficient to restore ISGylation, capsid assembly, and virion maturation. Consistent with these findings,\n                    <jats:italic toggle=\"yes\">A. actinomycetemcomitans<\/jats:italic>\n                    failed to enhance MHV68 lytic replication in ISG15-deficient MEFs. Extending this mechanism to representative herpesviruses, we showed that ISGylation of major capsid proteins is broadly required for efficient lytic replication. Together, these findings uncover a previously unrecognized strategy by which herpesviruses exploit an ISG15 innate immune effector, amplified by microbial coinfection, to promote virion assembly and productive infection.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeg7872","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:58:29Z","timestamp":1789149509000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Herpesviruses hijack ISGylation to promote viral capsid assembly"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7378-5740","authenticated-orcid":true,"given":"Shutong","family":"Li","sequence":"first","affiliation":[{"name":"Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5372-4497","authenticated-orcid":true,"given":"Shu","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Microbial Sciences in Health, Global Center for Pathogen and Human Health Research, Cleveland Clinic Research, Cleveland, OH 44106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1686-7752","authenticated-orcid":true,"given":"Yongzhen","family":"Liu","sequence":"additional","affiliation":[{"name":"Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0393-1751","authenticated-orcid":true,"given":"Chao","family":"Qin","sequence":"additional","affiliation":[{"name":"Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3847-8661","authenticated-orcid":true,"given":"Jianglin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeru","family":"Saito","sequence":"additional","affiliation":[{"name":"Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5703-2589","authenticated-orcid":true,"given":"Xinchi","family":"Xie","sequence":"additional","affiliation":[{"name":"Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Fu","sequence":"additional","affiliation":[{"name":"Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4119-8274","authenticated-orcid":true,"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biological Sciences, Dornsife College of Arts, Letters and Sciences, University of Southern California, Los Angeles, CA 90089, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenfeng","family":"Shu","sequence":"additional","affiliation":[{"name":"Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4477-1523","authenticated-orcid":true,"given":"Wayne","family":"Yeh","sequence":"additional","affiliation":[{"name":"Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, 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