Role of co-expressed APOBEC3F and APOBEC3G in inducing HIV-1 drug resistance. Issue 4 (April 2019)

• Record Type: Journal Article
• Authors: Mohammadzadeh, Nazanin; Love, Robin P.; Gibson, Richard; Arts, Eric J.; Poon, Art F.Y.; Chelico, Linda
• Is Part Of: Heliyon. Volume 5:Issue 4(2019)
• Publication Date: 2019-04
• Subjects: Immunology -- Microbiology; Research -- Periodicals; Medical sciences -- Periodicals; Natural history -- Periodicals; Social sciences -- Periodicals; Earth sciences -- Periodicals; Physical sciences -- Periodicals; 507.2
• DOI: 10.1016/j.heliyon.2019.e01498
• Languages: English
• ISSNs: 2405-8440

Abstract

Abstract: The APOBEC3 enzymes can induce mutagenesis of HIV-1 proviral DNA through the deamination of cytosine. HIV-1 overcomes this restriction through the viral protein Vif that induces APOBEC3 proteasomal degradation. Within this dynamic host-pathogen relationship, the APOBEC3 enzymes have been found to be beneficial, neutral, or detrimental to HIV-1 biology. Here, we assessed the ability of co-expressed APOBEC3F and APOBEC3G to induce HIV-1 resistance to antiviral drugs. We found that co-expression of APOBEC3F and APOBEC3G enabled partial resistance of APOBEC3F to Vif-mediated degradation with a corresponding increase in APOBEC3F-induced deaminations in the presence of Vif, in addition to APOBEC3G-induced deaminations. We recovered HIV-1 drug resistant variants resulting from APOBEC3-induced mutagenesis, but these variants were less able to replicate than drug resistant viruses derived from RT-induced mutations alone. The data support a model in which APOBEC3 enzymes cooperate to restrict HIV-1, promoting viral inactivation over evolution to drug resistance.