Vif is a RNA chaperone that could temporally regulate RNA dimerization and the early steps of HIV-1 reverse transcription.
HIV-1 Vif (viral infectivity factor) is associated with the assembly complexes and packaged at low level into the viral particles, and is essential for viral replication in non-permissive cells. Viral particles produced in the absence of Vif exhibit structural defects and are defective in the early steps of reverse transcription. Here, we show that Vif is able to anneal primer tRNA(Lys3) to the viral RNA, to decrease pausing of reverse transcriptase during (-) strand strong-stop DNA synthesis, and to promote the first strand transfer. Vif also stimulates formation of loose HIV-1 genomic RNA dimers. These results indicate that Vif is a bona fide RNA chaperone. We next studied the effects of Vif in the presence of HIV-1 NCp, which is a well-established RNA chaperone. Vif inhibits NCp-mediated formation of tight RNA dimers and hybridization of tRNA(Lys3), while it has little effects on NCp-mediated strand transfer and it collaborates with nucleocapsid (NC) to increase RT processivity. Thus, Vif might negatively regulate NC-assisted maturation of the RNA dimer and early steps of reverse transcription in the assembly complexes, but these inhibitory effects would be relieved after viral budding, thanks to the limited packaging of Vif in the virions.
Architecture et Réactivité de l'ARN, Université Louis Pasteur, CNRS, IBMC, 15 rue René Descartes, 67084, Strasbourg cedex, France.
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Henriet
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Sinck
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Bec
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Gorelick
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Marquet
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Paillart
D036022:Capsid Proteins / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000096:biosynthesis; D019281:Dimerization; D015683:Gene Products, gag / Q000378:metabolism; D016346:Gene Products, vif / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics*; D018832:Molecular Chaperones / Q000378:metabolism*; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D048348:Reverse Transcription; D014764:Viral Proteins / Q000378:metabolism; D054301:gag Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus
D036022:Capsid Proteins; D004277:DNA, Single-Stranded; D015683:Gene Products, gag; D016346:Gene Products, vif; D018832:Molecular Chaperones; C071884:NCP7 protein, Human immunodeficiency virus 1; D012346:RNA, Transfer, Amino Acyl; D012367:RNA, Viral; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus