Diversity of HIV-1 Vpr Interactions Involves Usage of the WXXF Motif of Host Cell Proteins

• Published in: The Journal of biological chemistry 1998-04, Vol.273 (14), p.8009-8016
• Main Authors: BouHamdan, M, Xue, Y, Baudat, Y, Hu, B, Sire, J, Pomerantz, R J, Duan, L X
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Amino Acid Sequence; Base Sequence; Binding Sites; Gene Products, vpr - physiology; HIV-1 - physiology; Humans; Molecular Sequence Data; Protein Binding; Proteins - genetics; Proteins - metabolism; Sequence Analysis; Virus Replication; vpr Gene Products, Human Immunodeficiency Virus
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.14.8009

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, W XX F. More importantly, we demonstrate that the W XX F motif of uracil DNA glycosylase is implicated in the interaction of uracil DNA glycosylase with Vpr intracellularly. Finally, a dimer of the W XX F motif was fused to the chloramphenicol acetyl transferase (CAT) gene, and it was demonstrated that the W XX F 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.