Different Mutagenic Potential of HIV-1 Restriction Factors APOBEC3G and APOBEC3F Is Determined by Distinct Single-Stranded DNA Scanning Mechanisms

• DOI: 10.1371/journal.ppat.1004024
• Publication Date: 2014-03-20T21:05:47Z
• Authors: Anjuman Ara; Robin P. Love; Linda Chelico
• Keywords: APOBEC3G

The APOBEC3 deoxycytidine deaminase family functions as host restriction factors that can block replication of Vif (virus infectivity factor) deficient HIV-1 virions to differing degrees by deaminating cytosines uracils in single-stranded (−)HIV-1 DNA. Upon the (−)DNA (+)DNA, reverse transcriptase incorporates adenines opposite uracils, thereby inducing C/G→T/A mutations functionally inactivate HIV-1. Although both APOBEC3F and APOBEC3G are expressed cell types infects suppressed Vif, there has been no prior biochemical analysis APOBEC3F, contrast APOBEC3G. Using synthetic DNA substrates, we characterized found similar APOBEC3G; it is a processive enzyme deaminate at least two single enzyme-substrate encounter. However, scanning movement distinct from APOBEC3G, relies on jumping rather than sliding. movements were also different lack sliding due an 190NPM192 motif, since insertion this motif into decreases its movements. NPM mutant induced significantly less comparison wild-type vitro model assay single-cycle assay, indicating differences relevant Conversely, mutation 191Pro 191Gly enables occur. 190NGM192 could slide, did not induce more mutagenesis demonstrating unique mechanism abrogates influence mutagenesis. Overall, demonstrate key impact APOBEC3F- APOBEC3G-induced supports which preferred deamination (APOBEC3F, 5′TTC; 5′CCC) influences mutagenic gene inactivation potential enzyme.