AKAP149 binds to HIV-1 reverse transcriptase and is involved in the reverse transcription

J Mol Biol. 2008 Nov 21;383(4):783-96. doi: 10.1016/j.jmb.2008.08.055. Epub 2008 Aug 29.


Like all retroviruses, human immunodeficiency virus type 1 (HIV-1) undergoes reverse transcription during its replication cycle. The cellular cofactors potentially involved in this process still remain to be identified. We show here that A-kinase anchoring protein 149 (AKAP149) interacts with HIV-1 reverse transcriptase (RT) in both the yeast two-hybrid system and human cells. The AKAP149 binding site has been mapped to the RNase H domain of HIV-1 RT. AKAP149 silencing by RNA interference in HIV-1-infected cells inhibited viral replication at the reverse transcription step. We selected single-point mutants of RT defective for AKAP149 binding and demonstrated that mutant G462R, despite retaining significant intrinsic RT activity in vitro, failed to carry out HIV-1 reverse transcription correctly in infected cells. This suggests that the interaction between RT and AKAP149 in infected cells may play an important role in HIV-1 reverse transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A Kinase Anchor Proteins / chemistry
  • A Kinase Anchor Proteins / genetics
  • A Kinase Anchor Proteins / metabolism*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Line
  • HIV Reverse Transcriptase / chemistry
  • HIV Reverse Transcriptase / genetics
  • HIV Reverse Transcriptase / metabolism*
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Interference
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Reverse Transcription / physiology*
  • Two-Hybrid System Techniques
  • Virion / metabolism
  • Virus Replication / physiology


  • A Kinase Anchor Proteins
  • AKAP1 protein, human
  • Recombinant Fusion Proteins
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase