{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:51:15Z","timestamp":1790664675337,"version":"4.1.0"},"reference-count":88,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,28]],"date-time":"2021-02-28T00:00:00Z","timestamp":1614470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family of DNA cytosine deaminases provides a broad and overlapping defense against viral infections. Successful viral pathogens, by definition, have evolved strategies to escape restriction by the APOBEC enzymes of their hosts. HIV-1 and related retroviruses are thought to be the predominant natural substrates of APOBEC enzymes due to obligate single-stranded (ss)DNA replication intermediates, abundant evidence for cDNA strand C-to-U editing (genomic strand G-to-A hypermutation), and a potent APOBEC degradation mechanism. In contrast, much lower mutation rates are observed in double-stranded DNA herpesviruses and the evidence for APOBEC mutation has been less compelling. However, recent work has revealed that Epstein-Barr virus (EBV), Kaposi\u2019s sarcoma-associated herpesvirus (KSHV), and herpes simplex virus-1 (HSV-1) are potential substrates for cellular APOBEC enzymes. To prevent APOBEC-mediated restriction these viruses have repurposed their ribonucleotide reductase (RNR) large subunits to directly bind, inhibit, and relocalize at least two distinct APOBEC enzymes\u2014APOBEC3B and APOBEC3A. The importance of this interaction is evidenced by genetic inactivation of the EBV RNR (BORF2), which results in lower viral infectivity and higher levels of C\/G-to-T\/A hypermutation. This RNR-mediated mechanism therefore likely functions to protect lytic phase viral DNA replication intermediates from APOBEC-catalyzed DNA C-to-U deamination. The RNR-APOBEC interaction defines a new pathogen-host conflict that the virus must win in real-time for transmission and pathogenesis. However, partial losses over evolutionary time may also benefit the virus by providing mutational fuel for adaptation.<\/jats:p>","DOI":"10.3390\/v13030390","type":"journal-article","created":{"date-parts":[[2021,2,28]],"date-time":"2021-02-28T20:43:32Z","timestamp":1614545012000},"page":"390","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["APOBECs and Herpesviruses"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6277-9433","authenticated-orcid":false,"given":"Adam Z.","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia N.","family":"Moraes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine M.","family":"Shaban","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2044-8473","authenticated-orcid":false,"given":"Elisa","family":"Fanunza","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7890-7409","authenticated-orcid":false,"given":"Craig J.","family":"Bierle","sequence":"additional","affiliation":[{"name":"Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Southern","sequence":"additional","affiliation":[{"name":"Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wade A.","family":"Bresnahan","sequence":"additional","affiliation":[{"name":"Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Rice","sequence":"additional","affiliation":[{"name":"Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reuben S.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Howard Hughes Medical Institute, University of Minnesota, Minneapolis, MN 55455, 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