{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:14:49Z","timestamp":1790781289779,"version":"4.1.0"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":213,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Nih","award":["AI132507 AI139106"],"award-info":[{"award-number":["AI132507 AI139106"]}]},{"name":"NFRFE","award":["2021-00933"],"award-info":[{"award-number":["2021-00933"]}]},{"name":"Nih","award":["AI132507 AI139106"],"award-info":[{"award-number":["AI132507 AI139106"]}]},{"name":"NFRFE","award":["2021-00933"],"award-info":[{"award-number":["2021-00933"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>APOBEC3, an enzyme subfamily that plays a role in virus restriction by generating mutations at particular DNA motifs or mutational \u2018hotspots\u2019, can drive viral mutagenesis with host-specific preferential hotspot mutations contributing to pathogen variation. While previous analysis of viral genomes from the 2022 Mpox (formerly Monkeypox) disease outbreak has shown a high frequency of C&amp;gt;T mutations at TC motifs, suggesting recent mutations are human APOBEC3-mediated, how emerging monkeypox virus (MPXV) strains will evolve as a consequence of APOBEC3-mediated mutations remains unknown. By measuring hotspot under-representation, depletion at synonymous sites, and a combination of the two, we analyzed APOBEC3-driven evolution in human poxvirus genomes, finding varying hotspot under-representation patterns. While the native poxvirus molluscum contagiosum exhibits a signature consistent with extensive coevolution with human APOBEC3, including depletion of TC hotspots, variola virus shows an intermediate effect consistent with ongoing evolution at the time of eradication. MPXV, likely the result of recent zoonosis, showed many genes with more TC hotspots than expected by chance (over-representation) and fewer GC hotspots than expected (under-representation). These results suggest the MPXV genome: (1) may have evolved in a host with a particular APOBEC GC hotspot preference, (2) has inverted terminal repeat (ITR) regions\u2014which may be exposed to APOBEC3 for longer during viral replication\u2014and longer genes likely to evolve faster, and therefore (3) has a heightened potential for future human APOBEC3-meditated evolution as the virus spreads in the human population. Our predictions of MPXV mutational potential can both help guide future vaccine development and identification of putative drug targets and add urgency to the task of containing human Mpox disease transmission and uncovering the ecology of the virus in its reservoir host.<\/jats:p>","DOI":"10.1093\/ve\/vead047","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T17:14:51Z","timestamp":1690391691000},"source":"Crossref","is-referenced-by-count":24,"title":["Evolutionary potential of\u00a0the monkeypox genome arising from interactions with human APOBEC3 enzymes"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8430-9238","authenticated-orcid":false,"given":"Brenda","family":"Delamonica","sequence":"first","affiliation":[{"name":"Department of Applied Mathematics and Statistics, Stony Brook University , Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4327-7697","authenticated-orcid":false,"given":"Liliana","family":"Davalos","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolution, Stony Brook University , Stony Brook, NY 11794, USA"},{"name":"Consortium for Inter-Disciplinary Environmental Research, Stony Brook University , Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mani","family":"Larijani","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Simon Fraser University , Burnaby, BC V5A 1S6, Canada"},{"name":"Department of Pathology, Microbiology, and Immunology, University of California-Davis School of Veterinary Medicine , Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J","family":"Anthony","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of California-Davis School of Veterinary Medicine , Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Arkansas for Medical Sciences (UAMS) , Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"MacCarthy","sequence":"additional","affiliation":[{"name":"Department of Applied Mathematics and Statistics, Stony Brook University , Stony Brook, NY 11794, USA"},{"name":"Laufer Center for Physical and Quantitative Biology, Stony Brook University , Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"key":"2023090904321995500_R1","doi-asserted-by":"crossref","first-page":"624","DOI":"10.4049\/jimmunol.160.2.624","article-title":"Blockade of\u00a0Chemokine Activity by a Soluble Chemokine Binding Protein from Vaccinia Virus","volume":"160","author":"Alcam\u00ed","year":"1998","journal-title":"The Journal of Immunology"},{"key":"2023090904321995500_R2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1093\/nar\/gkj416","article-title":"APOBEC3A and\u00a0APOBEC3B are Potent Inhibitors of\u00a0LTR-retrotransposon Function in\u00a0Human Cells","volume":"34","author":"Bogerd","year":"2006","journal-title":"Nucleic Acids Research"},{"key":"2023090904321995500_R3","article-title":"Possible Adaption of\u00a0the 2022 Monkeypox Virus to the Human Host through Gene Duplication 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