Role of co-expressed APOBEC3F and APOBEC3G in inducing HIV-1 drug resistance
Nazanin Mohammadzadeh,
Robin P. Love,
Richard Gibson,
Eric J. Arts,
Art F.Y. Poon,
Linda Chelico
Affiliations
Nazanin Mohammadzadeh
University of Saskatchewan, Biochemistry, Microbiology, and Immunology, College of Medicine, Saskatoon, Saskatchewan, S7H 5E5, Canada
Robin P. Love
University of Saskatchewan, Biochemistry, Microbiology, and Immunology, College of Medicine, Saskatoon, Saskatchewan, S7H 5E5, Canada
Richard Gibson
Western University, Schulich School of Medicine and Dentistry, Department of Microbiology and Immunology, London, Ontario, N6A 5C1, Canada
Eric J. Arts
Western University, Schulich School of Medicine and Dentistry, Department of Microbiology and Immunology, London, Ontario, N6A 5C1, Canada
Art F.Y. Poon
Western University, Schulich School of Medicine and Dentistry, Department of Microbiology and Immunology, London, Ontario, N6A 5C1, Canada; Western University, Schulich School of Medicine and Dentistry, Department of Pathology and Laboratory Medicine, London, Ontario, N6A 5C1, Canada
Linda Chelico
University of Saskatchewan, Biochemistry, Microbiology, and Immunology, College of Medicine, Saskatoon, Saskatchewan, S7H 5E5, Canada; Corresponding author.
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.
