title: Differential incorporation of uracil DNA glycosylase UNG2 into HIV-1, HIV-2, and SIV(MAC) viral particles.
abstract: We have previously reported that the host uracil DNA glycosylase UNG2 enzyme is incorporated into HIV-1 virions via a specific association with the viral integrase (IN) domain of Gag-Pol precursor. In this study, we investigated whether UNG2 was packaged into two phylogenetically closely related primate lentiviruses, HIV-2(ROD) and SIV(MAC239). We demonstrated by GST-pull-down and coprecipitation assays that INs from HIV-1, HIV-2(ROD), and SIV(MAC239) associated with UNG2, although the interaction of UNG2 with HIV-2(ROD) IN and SIV(MAC239) IN was less strong than with HIV-1 IN. We then showed by Western blotting that highly purified HIV-2 and SIV(MAC) viral particles did not incorporate host UNG2, contrasting with the presence of UNG2 in HIV-1 viral particles. Finally, we showed that HIV-1/SIV chimeric viruses in which residues 6 to 202 of HIV-1 IN were replaced by the SIV counterpart were impaired for packaging of UNG2, indicating that the incorporation of host UNG2 into viral particles is the hallmark of the HIV-1 strain. Moreover, we found that HIV-1/SIV IN chimeric viruses were deficient for viral propagation.
authors.affiliation: Pathogénie des Infections à Lentivirus, INSERM U372, Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Priet
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Navarro
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gros
authors.forename: Gilles
authors.initials: G
authors.lastname: Quérat
authors.forename: Joséphine
authors.initials: J
authors.lastname: Sire
mesh_terms: D002478:Cells, Cultured; D045647:DNA Glycosylases; D015497:HIV-1 / Q000378:metabolism*; D015498:HIV-2 / Q000378:metabolism*; D006801:Humans; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D051981:Uracil-DNA Glycosidase; D014771:Virion / Q000378:metabolism*
chemical_list: D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase