title: AKAP149 binds to HIV-1 reverse transcriptase and is involved in the reverse transcription.
abstract: 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.
authors.affiliation: Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Lemay
authors.forename: Priscilla
authors.initials: P
authors.lastname: Maidou-Peindara
authors.forename: Reynel
authors.initials: R
authors.lastname: Cancio
authors.forename: Eric
authors.initials: E
authors.lastname: Ennifar
authors.forename: Gaël
authors.initials: G
authors.lastname: Coadou
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maga
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Rain
authors.forename: Richard
authors.initials: R
authors.lastname: Benarous
authors.forename: Lang Xia
authors.initials: LX
authors.lastname: Liu
mesh_terms: D054758:A Kinase Anchor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D048348:Reverse Transcription / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D014771:Virion / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology
chemical_list: D054758:A Kinase Anchor Proteins; C105137:AKAP1 protein, human; D011993:Recombinant Fusion Proteins; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase