The cellular antiviral protein APOBEC3G interacts with HIV-1 reverse transcriptase and inhibits its function during viral replication

J Virol. 2012 Apr;86(7):3777-86. doi: 10.1128/JVI.06594-11. Epub 2012 Feb 1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC-3G Deaminase
  • Amino Acid Motifs
  • Cell Line
  • Cytidine Deaminase / chemistry
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / metabolism*
  • Down-Regulation
  • HIV Infections / enzymology*
  • HIV Infections / genetics
  • HIV Infections / virology
  • HIV Reverse Transcriptase / genetics
  • HIV Reverse Transcriptase / metabolism*
  • HIV-1 / enzymology*
  • HIV-1 / genetics
  • HIV-1 / physiology
  • Humans
  • Protein Binding
  • Virus Replication*

Substances

  • HIV Reverse Transcriptase
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human
  • Cytidine Deaminase