The Multimerization of Human Immunodeficiency Virus Type I Vif Protein

Abstract

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 pe-ripheral blood mononuclear cells, macrophages, and H9 T-cells. However, the molecular mechanism(s) of Vif re-mains unknown and needs to be further determined. In this report, we show that, like many other proteins en-coded 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 mamma-lian 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-defec-tive 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 iden-tified a new feature of Vif and should accelerate our understanding of its role in HIV-1 pathogenesis.