title: Sequence and structure requirements for specific recognition of HIV-1 TAR and DIS RNA by the HIV-1 Vif protein.
abstract: The HIV-1 Vif protein plays an essential role in the regulation of the infectivity of HIV-1 virion and in vivo pathogenesis. Vif neutralizes the human DNA-editing enzyme APOBEC3 protein, an antiretroviral cellular factor from the innate immune system, allowing the virus to escape the host defence system. It was shown that Vif is packaged into viral particles through specific interactions with the viral genomic RNA. Conserved and structured sequences from the 5'-noncoding region, such as the Tat-responsive element (TAR) or the genomic RNA dimerization initiation site (DIS), are primary binding sites for Vif. In the present study we used isothermal titration calorimetry to investigate sequence and structure determinants important for Vif binding to short viral RNA corresponding to TAR and DIS stem-loops. We showed that Vif specifically binds TAR and DIS in the low nanomolar range. In addition, Vif primarily binds the TAR UCU bulge, but not the apical loop. Determinants for Vif binding to the DIS loop-loop complex are likely more complex and involve the self-complementary loop together with the upper part of the stem. These results suggest that Tat-TAR inhibitors or DIS small molecule binders might be also effective to disturb Vif-TAR and Vif-DIS binding in order to reduce Vif packaging into virions.
authors: Architecture et Réactivité des ARN, CNRS/Université de Strasbourg, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors: Séverine
authors: S
authors: Freisz
authors: Joelle
authors: J
authors: Mezher
authors: Lamine
authors: L
authors: Hafirassou
authors: Philippe
authors: P
authors: Wolff
authors: Yves
authors: Y
authors: Nominé
authors: Christophe
authors: C
authors: Romier
authors: Philippe
authors: P
authors: Dumas
authors: Eric
authors: E
authors: Ennifar
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002151:Calorimetry; D004926:Escherichia coli / Q000235:genetics; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D055029:Inverted Repeat Sequences; D010316:Particle Size; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012338:RNA, Ribosomal, 23S / Q000737:chemistry / Q000235:genetics; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000737:chemistry*
chemical_list: D012338:RNA, Ribosomal, 23S; D012367:RNA, Viral; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1