The cellular antiviral protein APOBEC3G interacts with HIV-1 reverse transcriptase and inhibits its function during viral replication.
The cytidine deaminase APOBEC3G (A3G) exerts a multifaceted antiviral effect against HIV-1 infection. First, A3G was shown to be able to terminate HIV infection by deaminating the cytosine residues to uracil in the minus strand of the viral DNA during reverse transcription. Also, a number of studies have indicated that A3G inhibits HIV-1 reverse transcription by a non-editing-mediated mechanism. However, the mechanism by which A3G directly disrupts HIV-1 reverse transcription is not fully understood. In the present study, by using a cell-based coimmunoprecipitation (Co-IP) assay, we detected the direct interaction between A3G and HIV-1 reverse transcriptase (RT) in produced viruses and in the cotransfected cells. The data also suggested that their interaction did not require viral genomic RNA bridging or other viral proteins. Additionally, a deletion analysis showed that the RT-binding region in A3G was located between amino acids 65 and 132. Overexpression of the RT-binding polypeptide A3G(65-132) was able to disrupt the interaction between wild-type A3G and RT, which consequently attenuated the anti-HIV effect of A3G on reverse transcription. Overall, this paper provides evidence for the physical and functional interaction between A3G and HIV-1 RT and demonstrates that this interaction plays an important role in the action of A3G against HIV-1 reverse transcription.
Laboratory of Molecular Human Retrovirologya and Department of Medical Microbiology,b Faculty of Medicine, University of Manitoba, Winnipeg, Canada. yao2@cc.umanitoba.ca
Xiaoxia
X
Wang
Zhujun
Z
Ao
Liyu
L
Chen
Gary
G
Kobinger
Jinyu
J
Peng
Xiaojian
X
Yao
D000071480:APOBEC-3G Deaminase; D020816:Amino Acid Motifs; D002460:Cell Line; D003564:Cytidine Deaminase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015658:HIV Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D006801:Humans; D011485:Protein Binding; D014779:Virus Replication
D054303:HIV Reverse Transcriptase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase