Uracils as a cellular weapon against viruses and mechanisms of viral escape.
Uracil in DNA is a deleterious event that may arise either by cytosine deamination or misincorporation of dUTP. Consequently, cells from all free-living organisms have developed strategies to protect their genome against the presence of uracils, by using uracil DNA glycosylase (UNG) and deoxyuridine triphosphatase (dUTPase) enzymatic activities. In the viral kingdom, some (namely poxviruses and herpesviruses) but not all of the DNA viruses encode their own UNG and dUTPase to control uracilation of their genome. Some retroviruses, which are RNA viruses using DNA as an intermediate of replication, also encode dUTPase. Surprisingly, though most of nonprimate lentiviruses encode dUTPase, primate lentiviruses such as HIV-1, HIV-2 or SIV do not. Because these latter viruses also replicate in nondividing cells where the dUTP/dTTP ratio is high, it is probable that they have found other ways to fight against the emergence of uracilated-viral transcripts. Indeed, recent studies showed that HIV-1 efficiently controls both the cytosine deamination and the dUTP misincorporation. The viral Vif protein acts in preventing the packaging into viral particles of the host-derived cytosine deaminase APOBEC3G enzyme, while the viral integrase domain of the Gag-Pol precursor mediates the packaging of the host-derived uracil DNA glycosylase UNG2 enzyme. In the absence of Vif or UNG2, HIV-1 viral transcripts are heavily charged in uracil bases leading to inactivation of the virus.
Priet
Stéphane
S
Unitédes Virus Emergents, Facultéde Médecine, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France.
Sire
Joséphine
J
Quérat
Gilles
G
D004279:DNA, Viral / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D006801:Humans; D012190:Retroviridae / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D014498:Uracil / Q000378:metabolism* / Q000494:pharmacology; D051981:Uracil-DNA Glycosidase / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects*
D004279:DNA, Viral; D014498:Uracil; D051981:Uracil-DNA Glycosidase