title: Formation of immature and mature genomic RNA dimers in wild-type and protease-inactive HIV-1: differential roles of the Gag polyprotein, nucleocapsid proteins NCp15, NCp9, NCp7, and the dimerization initiation site.
abstract: Formation of immature genomic RNA (gRNA) dimers is exquisitely nucleocapsid (NC)-dependent in protease-inactive (PR-in) HIV-1. This establishes that Pr55gag/Pr160gag-pol has NC-dependent chaperone activity within intact HIV-1. Mutations in the proximal zinc finger and the linker of the NC sequence of Pr55gag/Pr160gag-pol abolish gRNA dimerization in PR-in HIV-1. In wild type, where the NC of Pr55gag is processed into progressively smaller proteins termed NCp15 (NCp7-p1-p6), NCp9 (NCp7-p1) and NCp7, formation of immature dimers is much swifter than in PR-in HIV-1. NCp7 and NCp15 direct this rapid accumulation. NCp9 is sluggish in this process, but it stimulates the transition from immature to mature gRNA dimer as well as NCp7 and much better than NCp15. The amino-terminus, proximal zinc finger, linker, and distal zinc finger of NCp7 contribute to this maturation event in intact HIV-1. The DIS is a dimerization initiation site for all immature gRNA dimers, irrespective of their mechanism of formation.
authors.affiliation: McGill AIDS Center, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal QC, Canada H3T 1E2.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Jalalirad
authors.forename: Michael
authors.initials: M
authors.lastname: Laughrea
mesh_terms: D019281:Dimerization; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D016679:Genome, Viral; D016333:HIV Protease / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
chemical_list: D015683:Gene Products, gag; C071884:NCP7 protein, Human immunodeficiency virus 1; D019590:Nucleocapsid Proteins; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus; C060295:p15 gag protein, Human immunodeficiency virus 1; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1