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Previous studies have demonstrated that the apolipoprotein B mRNA editing enzyme polypeptide-like 3 (APOBEC3, A3) family of proteins (at least A3D, A3F, A3G, and stable A3H haplotypes) contribute to HIV-1 restriction in CD4\n            <jats:sup>+<\/jats:sup>\n            T lymphocytes. Virus-encoded virion infectivity factor (Vif) counteracts this antiviral activity by degrading A3 enzymes allowing HIV-1 replication in infected cells. In addition to A3 proteins, Vif also targets other cellular proteins in CD4\n            <jats:sup>+<\/jats:sup>\n            T lymphocytes, including PPP2R5 proteins. However, whether Vif primarily degrades only A3 proteins during viral replication is currently unknown. Herein, we describe the development and characterization of\n            <jats:italic>A3F<\/jats:italic>\n            -,\n            <jats:italic>A3F\/A3G<\/jats:italic>\n            -, and\n            <jats:italic>A3A<\/jats:italic>\n            -to-\n            <jats:italic>A3G<\/jats:italic>\n            -null THP-1 cells. In comparison to Vif-proficient HIV-1, Vif-deficient viruses have substantially reduced infectivity in parental and\n            <jats:italic>A3F<\/jats:italic>\n            -null THP-1 cells, and a more modest decrease in infectivity in\n            <jats:italic>A3F\/A3G<\/jats:italic>\n            -null cells. Remarkably, disruption of A3A\u2013A3G protein expression completely restores the infectivity of Vif-deficient viruses in THP-1 cells. These results indicate that the primary function of Vif during infectious HIV-1 production from THP-1 cells is the targeting and degradation of A3 enzymes.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              HIV-1 Vif neutralizes the HIV-1 restriction activity of A3 proteins. However, it is currently unclear whether Vif has additional essential cellular targets. To address this question, we disrupted\n              <jats:italic>A<\/jats:italic>\n              3\n              <jats:italic>A<\/jats:italic>\n              to\n              <jats:italic>A<\/jats:italic>\n              3\n              <jats:italic>G<\/jats:italic>\n              genes in the THP-1 myeloid cell line using CRISPR and compared the infectivity of wild-type HIV-1 and Vif mutants with the selective A3 neutralization activities. Our results demonstrate that the infectivity of Vif-deficient HIV-1 and the other Vif mutants is fully restored by ablating the expression of cellular A3A to A3G proteins. These results indicate that A3 proteins are the only essential target of Vif that is required for fully infectious HIV-1 production from THP-1 cells.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.00782-23","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T13:00:40Z","timestamp":1691586040000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["APOBEC3 degradation is the primary function of HIV-1 Vif determining virion infectivity in the myeloid cell line THP-1"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2869-9450","authenticated-orcid":true,"given":"Terumasa","family":"Ikeda","sequence":"first","affiliation":[{"name":"Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus Infection, Kumamoto University , Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus Infection, Kumamoto University , Kumamoto, Japan"},{"name":"Graduate School of Medical Sciences, Kumamoto University , Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesham","family":"Nasser","sequence":"additional","affiliation":[{"name":"Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus Infection, Kumamoto University , Kumamoto, Japan"},{"name":"Department of Clinical Pathology, Faculty of Medicine, Suez Canal University , Ismailia, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Structural Biology, University of Texas Health San Antonio , San Antonio, Texas, USA"},{"name":"Howard Hughes Medical Institute, University of Texas Health San Antonio , San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6277-9433","authenticated-orcid":true,"given":"Adam Z.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota , Minneapolis, Minnesota, USA"},{"name":"Institute for Molecular Virology, University of Minnesota , Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota , Minneapolis, Minnesota, USA"},{"name":"Institute for Molecular Virology, University of Minnesota , Minneapolis, Minnesota, 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