HIV-1 Subtype Variability in Vif Derived from Molecular Clones Affects APOBEC3G-Mediated Host Restriction

• Published in: Intervirology Vol. 56; no. 4; pp. 258 - 264
• Main Authors: Lisovsky, Irene, Schader, Susan M., Sloan, Richard D., Oliveira, Maureen, Coutsinos, Dimitrios, Bernard, Nicole F., Wainberg, Mark A.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2013
• Subjects: APOBEC-3G Deaminase; Cell Line; Cytidine Deaminase - immunology; Cytidine Deaminase - metabolism; Genetic Variation; HIV-1 - genetics; HIV-1 - immunology; HIV-1 - physiology; Human immunodeficiency virus 1; Humans; Short Communication; vif Gene Products, Human Immunodeficiency Virus - genetics; vif Gene Products, Human Immunodeficiency Virus - metabolism; Virus Replication; Viral infectivity; HIV-1 subtype diversity; Vif; APOBEC3G
• ISSN: 0300-5526; 1423-0100; 1423-0100
• DOI: 10.1159/000348513

Background: The host protein APOBEC3G (A3G) can limit HIV-1 replication. Its protective effect is overcome by the HIV-1 ‘viral infectivity factor' (Vif), which targets A3G for proteosomal degradation. Although Vif is considered to be essential for HIV-1 replication, the effect of Vif variability among commonly used HIV-1 molecular clones of different genetic backgrounds on viral infectiousness and pathogenesis has not been fully determined. Methods: We cloned the intact Vif coding regions of available molecular clones of different subtypes into expression vectors. Δvif full-length HIV-1 clonal variants were generated from corresponding subtype-specific full-length molecular clones. Replication-competent viruses were produced in 293T cells in the presence or absence of A3G, with Vif being supplied by the full-length HIV-1 clone or in trans. The extent of A3G-mediated restriction was then determined in a viral replication assay using a reporter cell line. Results and Conclusions: In the absence of A3G, Vif subtype origin did not impact viral replication. In the presence of A3G the subtype origin of Vif had a differential effect on viral replication. Vif derived from a subtype C molecular clone was less effective at overcoming A3G-mediated inhibition than Vif derived from either subtype B or CRF02_AG molecular clones.