DNA repair enzyme uracil DNA glycosylase is specifically incorporated intohuman immunodeficiency virus type 1 viral particles through a Vpr-independent mechanism

The Vpr protein, encoded by the human immunodeficiency virus type 1 (HIV-1) genome, is one of the nonstructural proteins packaged in large amounts int o viral particles. We have previously reported that Vpr associates with the DNA repair enzyme uracil DNA glycosylase (UDG). In this study, we extended these observations by investigating whether UDG is incorporated into virio ns and whether this incorporation requires the presence of Vpr. Our results , with highly purified viruses, show that UDG is efficiently incorporated e ither into wild-type virions or into Vpr-deficient HIV-1 virions, indicatin g that Vpr is not involved in UDG packaging. Using an in vitro protein-prot ein binding assay, we reveal a direct interaction between the precursor for m of UDG and the viral integrase (IN). Finally,we demonstrate that IN-defec tive viruses fail to incorporate UDG, indicating that IN is required for pa ckaging of UDG into virions.