{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T18:57:17Z","timestamp":1757703437299,"version":"3.41.2"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["R01 CA058376"],"award-info":[{"award-number":["R01 CA058376"]}]},{"name":"HHS | National Institutes of Health","award":["T32 AI060519"],"award-info":[{"award-number":["T32 AI060519"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,1,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The papillomavirus (PV) E2 protein is highly conserved, consisting of an N-terminal transactivation domain linked to a C-terminal DNA binding and dimerization domain (DBD) by a flexible hinge region. The E2 DBD exhibits a helix-turn-helix structure that dimerizes into a beta barrel prior to binding DNA; the first helix, \u03b11, is responsible for recognition of the palindromic E2 binding site. The DNA recognition helix consists of a tract of basic amino acids with a highly conserved central cysteine residue. Previous mutational analysis studies on this conserved cysteine have found that it is not required for viral replication or DNA binding. To investigate the function of this conserved cysteine\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              , we generated point mutations in MmuPV1 E2 at cysteine 307. We report here that this cysteine in the DNA recognition helix is required for transient viral replication and transactivation of proximal promoters, but C307 point mutants are still capable of enhancing the activation of distant upstream promoters\n              <jats:italic>in vitro<\/jats:italic>\n              . MmuPV1 genomes with the C307 mutation failed to produce warts when injected into mice, suggesting that the DNA recognition cysteine is required for viral replication\n              <jats:italic>in vivo<\/jats:italic>\n              .\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Papillomaviruses are the etiological agents of cancers of the oropharynx and anogenital tract. Understanding the mechanisms underlying PV pathogenesis is complicated by the strict species tropism displayed by the virus. The research presented here is significant because it links\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              models investigating the role of a conserved cysteine in the MmuPV1 E2 protein. This work elucidates the molecular mechanisms that regulate PV transcription and DNA replication and how these contribute to disease progression.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.01423-24","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T14:03:16Z","timestamp":1734012196000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["A conserved cysteine in the DNA-binding domain of MmuPV1 E2 is required for replication\n            <i>in vivo<\/i>"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8276-1580","authenticated-orcid":false,"given":"Jessica","family":"Gonzalez","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine","place":["Indianapolis, 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