title: Diversity of HIV-1 Vpr interactions involves usage of the WXXF motif of host cell proteins.
abstract: Targeting protein or RNA moieties to specific cellular compartments may enhance their desired functions and specificities. Human immunodeficiency virus type I (HIV-1) encodes proteins in addition to Gag, Pol, and Env that are packaged into virus particles. One such retroviral-incorporated protein is Vpr, which is present in all primate lentiviruses. Vpr has been implicated in different roles within the HIV-1 life cycle. In testing a new hypothesis in which viral proteins are utilized as docking sites to incorporate protein moieties into virions, we used the peptide phage display approach to search for Vpr-specific binding peptides. In the present studies, we demonstrate that most of the peptides that bind to Vpr have a common motif, WXXF. More importantly, we demonstrate that the WXXF motif of uracil DNA glycosylase is implicated in the interaction of uracil DNA glycosylase with Vpr intracellularly. Finally, a dimer of the WXXF motif was fused to the chloramphenicol acetyl transferase (CAT) gene, and it was demonstrated that the WXXF dimer-CAT fusion protein construct produces CAT activity within virions in the presence of Vpr as a docking protein. This study provides a novel potential strategy in the targeting of anti-viral agents to interfere with HIV-1 replication.
authors.affiliation: The Dorrance H. Hamilton Laboratories, Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: M
authors.initials: M
authors.lastname: BouHamdan
authors.forename: Y
authors.initials: Y
authors.lastname: Xue
authors.forename: Y
authors.initials: Y
authors.lastname: Baudat
authors.forename: B
authors.initials: B
authors.lastname: Hu
authors.forename: J
authors.initials: J
authors.lastname: Sire
authors.forename: R J
authors.initials: RJ
authors.lastname: Pomerantz
authors.forename: L X
authors.initials: LX
authors.lastname: Duan
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D016336:Gene Products, vpr / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D017421:Sequence Analysis; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D016336:Gene Products, vpr; D011506:Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus