Vif and the p55(Gag) polyprotein of human immunodeficiency virus type 1 are present in colocalizing membrane-free cytoplasmic complexes

The Vif protein of human immunodeficiency virus type 1 (HIV-1) is a potent regulator of viral infectivity. Current data posit that Vif functions late in replication to modulate assembly, budding, and/or maturation. Consistent with this model, earlier indirect immunofluorescence analyses of HIV-l-inf ected cells demonstrated that Vif and Gag colocalize to a substantial degre e (J.H.M. Simon, RA.M. Fouchier, T.E. Southerling, C.B. Guerra, C.K. Grant, and M.H. Malim,.J. Virol. 71:5259-5267, 1997). Here, we describe a series of subcellular fractionation studies which indicate that Vif and the p55(Ga g) polyprotein are present in membrane-free cytoplasmic complexes that copu rify in sucrose density gradients and are stable in nonionic detergents. Bo th Vif and Gag are targeted to these complexes independent of each other, a nd their association with them appears to be mediated by protein-protein in teractions. We propose that these complexes may represent viral assembly in termediates and that Vif is appropriately localized to influence the final stages of the viral life cycle and, therefore, the infectivity of progeny v irions.