{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:29:25Z","timestamp":1772162965801,"version":"3.50.1"},"reference-count":79,"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":"Canadian Government | Canadian Institutes of Health Research","award":["PJT-162407"],"award-info":[{"award-number":["PJT-162407"]}]},{"DOI":"10.13039\/501100000106","name":"Saskatchewan Health Research Foundation","doi-asserted-by":"crossref","award":["Postdoctoral Fellowship"],"award-info":[{"award-number":["Postdoctoral Fellowship"]}],"id":[{"id":"10.13039\/501100000106","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Saskatchewan College of Medicine","award":["Graduate Scholarship"],"award-info":[{"award-number":["Graduate Scholarship"]}]}],"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>Several APOBEC3 enzymes restrict HIV-1 by deaminating cytosine to form uracil in single-stranded proviral (\u2212)DNA. However, HIV-1 Vif counteracts their activity by inducing their proteasomal degradation. This counteraction by Vif is incomplete, as evidenced by footprints of APOBEC3-mediated mutations within integrated proviral genomes of people living with HIV-1. The relative contributions of multiple APOBEC3s in HIV-1 restriction are not fully understood. Here, we investigated the activity of co-expressed APOBEC3F and APOBEC3G against HIV-1 Subtype B and Subtype C transmitted\/founder viruses. We determined that APOBEC3F interacts with APOBEC3G through its N-terminal domain. We provide evidence that this results in protection of APOBEC3F from Vif-mediated degradation because the APOBEC3F N-terminal domain contains residues required for recognition by Vif. We also found that HIV-1 Subtype C Vifs, but not Subtype B Vifs, were less active against APOBEC3G when APOBEC3F and APOBEC3G were co-expressed. Consequently, when APOBEC3F and APOBEC3G were expressed together in a single cycle of HIV-1 replication, only HIV-1 Subtype C viruses showed a decrease in relative infectivity compared to when APOBEC3G was expressed alone. Inspection of Vif amino acid sequences revealed that differences in amino acids adjacent to conserved sequences influenced the Vif-mediated APOBEC3 degradation ability. Altogether, the data provide a possible mechanism for how combined expression of APOBEC3F and APOBEC3G could contribute to mutagenesis of HIV-1 proviral genomes despite the presence of Vif and provide evidence for variability in the Vif-mediated APOBEC3 degradation ability of transmitted\/founder viruses.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>APOBEC3 enzymes suppress HIV-1 infection by inducing cytosine deamination in proviral DNA but are hindered by HIV-1 Vif, which leads to APOBEC3 proteasomal degradation. Moving away from traditional studies that used lab-adapted HIV-1 Subtype B viruses and singular APOBEC3 enzymes, we examined how transmitted\/founder isolates of HIV-1 replicated in the presence of APOBEC3F and APOBEC3G. We determined that APOBEC3F interacts with APOBEC3G through its N-terminal domain and that APOBEC3F, like APOBEC3G, has Vif-mediated degradation determinants in the N-terminal domain. This enabled APOBEC3F to be partially resistant to Vif-mediated degradation. We also demonstrated that Subtype C is more susceptible than Subtype B HIV-1 to combined APOBEC3F\/APOBEC3G restriction and identified Vif variations influencing APOBEC3 degradation ability. Importantly, Vif amino acid variation outside of previously identified conserved regions mediated APOBEC3 degradation and HIV-1 Vif subtype-specific differences. Altogether, we identified factors that affect susceptibility to APOBEC3F\/APOBEC3G restriction.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01606-24","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T09:00:31Z","timestamp":1734944431000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Variability in HIV-1 transmitted\/founder virus susceptibility to combined APOBEC3F and APOBEC3G host restriction"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8939-8101","authenticated-orcid":true,"given":"Amit","family":"Gaba","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Microbiology, and Immunology, College of Medicine, University of Saskatchewan","place":["Saskatoon, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Yousefi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology, and Immunology, College of Medicine, University of Saskatchewan","place":["Saskatoon, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shreoshri","family":"Bhattacharjee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology, and Immunology, College of Medicine, University of Saskatchewan","place":["Saskatoon, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4673-8978","authenticated-orcid":true,"given":"Linda","family":"Chelico","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology, and Immunology, College of Medicine, University of Saskatchewan","place":["Saskatoon, 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