Differential incorporation of uracil DNA glycosylase UNG2 into HIV-1, HIV-2, and SIV(MAC) viral particles

Virology. 2003 Mar 15;307(2):283-9. doi: 10.1016/s0042-6822(02)00073-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • DNA Glycosylases*
  • HIV-1 / metabolism*
  • HIV-2 / metabolism*
  • Humans
  • N-Glycosyl Hydrolases / metabolism*
  • Simian Immunodeficiency Virus / metabolism*
  • Uracil-DNA Glycosidase
  • Virion / metabolism*

Substances

  • DNA Glycosylases
  • N-Glycosyl Hydrolases
  • Uracil-DNA Glycosidase