The multimerization of human immunodeficiency virus type I Vif protein: a requirement for Vif function in the viral life cycle.
The Vif (virion infectivity factor protein of human immunodeficiency virus type I (HIV-1) is essential for viral replication in vivo and productive infection of peripheral blood mononuclear cells, macrophages, and H9 T-cells. However, the molecular mechanism(s) of Vif remains unknown and needs to be further determined. In this report, we show that, like many other proteins encoded by HIV-1, Vif proteins possess a strong tendency toward self-association. In relatively native conditions, Vif proteins formed multimers in vitro, including dimers, trimers, or tetramers. Through in vivo binding assays such as coimmunoprecipitation and the mammalian two-hybrid system, we also demonstrated that Vif proteins could interact with each other within a cell, indicating that the multimerization of Vif proteins is not simply due to fortuitous aggregation. Further studies indicated that the domain affecting Vif self-association is located at the C terminus of this protein, especially the proline-enriched 151-164 region. Moreover, we found that a Vif mutant with deletion at amino acid 151-164 was unable to rescue the infectivity of vif-defective viruses generated from H9 T-cells, suggesting that the multimerization of Vif proteins could be important for Vif function in the viral life cycle. Our studies identified a new feature of Vif and should accelerate our understanding of its role in HIV-1 pathogenesis.
Yang
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Dorrance H. Hamilton Laboratories, Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Thomas Jefferson University, 1020 Locust St., Philadelphia, PA 19107, USA.
Sun
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Zhang
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D000818:Animals; D019556:COS Cells; D002460:Cell Line; D019281:Dimerization; D016346:Gene Products, vif / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000254:growth & development*; D009154:Mutation; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D014162:Transfection; D020798:Two-Hybrid System Techniques; D054320:vif Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D054320:vif Gene Products, Human Immunodeficiency Virus