{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:37:44Z","timestamp":1793129864764,"version":"4.5.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI184716, AG088625, AG070904, CA285192"],"award-info":[{"award-number":["AI184716, AG088625, AG070904, CA285192"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Cellular metabolic enzymes are well defined for their roles in metabolism, and their function beyond metabolism is poorly defined. Here, we report that herpes simplex virus 1 (HSV-1) couples evasion of the inflammatory response to metabolic activation to promote lytic replication. Specifically, HSV-1 activates carbamoyl-phosphate synthetase, aspartate transcarbamoylase, and dihydroorotase (CAD), which catalyzes the rate-limiting steps of\n                      <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                      pyrimidine synthesis. Activated CAD not only fuels\n                      <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                      nucleotide synthesis but also deamidates RelA. RelA deamidation suppresses NF-\u03baB activation and the inflammatory response while simultaneously upregulating key glycolytic enzymes to promote aerobic glycolysis. Further affinity purification and functional assays identified HSV-1 UL42 and UL47 that interact with and activate CAD, recapitulating the phenotypes of RelA deamidation. Collectively, our work uncovers a role for a metabolic enzyme in coupling immune evasion to metabolic activation through its protein deamidase activity during HSV-1 infection, highlighting a potential therapeutic target.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Host immune defense and cellular metabolism are two fundamental processes that shape viral pathogenesis. Here, we revealed that herpes simplex virus 1 (HSV-1) activates a nucleotide synthetic enzyme not only to support nucleotide synthesis but also to exploit its unconventional activity for immune evasion and metabolic reprogramming, highlighting a potential therapeutic target.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00920-26","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:03:45Z","timestamp":1790255025000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["HSV-1 UL42 and UL47 hijack cellular nucleotide synthetic enzyme CAD to promote lytic replication"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0393-1751","authenticated-orcid":true,"given":"Chao","family":"Qin","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Section of Infection and Immunity, Herman Ostrow School of Dentistry, University of Southern California","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinchi","family":"Xie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Section of Infection and Immunity, Herman Ostrow School of Dentistry, University of Southern California","place":["Los Angeles, 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