AKAP149 Binds to HIV-1 Reverse Transcriptase and Is Involved in the Reverse Transcription

作者：Lemay Julie; Maidou Peindara Priscilla; Cancio Reynel; Ennifar Eric; Coadou Gael; Maga Giovanni; Rain Jean Christophe; Benarous Richard^*; Liu Lang Xia

来源：Journal of Molecular Biology, 2008, 383(4): 783-796.

DOI：10.1016/j.jmb.2008.08.055

• AKAP149
• reverse transcriptase
• HIV-1
• PKA
• siRNA
• mutagenesis

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.

• 出版日期2008-11-21