The Vif (viral infectivity factor) protein of human immunodeficiency v
irus type 1 (HIV-1) has been shown to dramatically enhance the infecti
vity of HIV-1 virus particles during virus production. The subcellular
localization of Vif was examined to elucidate cellular pathways which
may be important far Vif function. Indirect immunofluorescence staini
ng of Vif demonstrated a diffuse cytoplasmic distribution and showed t
hat most Vif was not associated with the Golgi complex, a proposed sit
e of localization (B. Guy, M. Geist, K. Dott, D. Spehner, M.-P. Kieny,
and J.-P. Lecocq, J. Virol. 65:1325-1331, 1991). Subcellular fraction
ation of transfected COS cells and HIV-1-infected Jurkat and CEM cells
demonstrated that Vif is a cytoplasmic protein which exists in both a
soluble cytosolic form and membrane-associated form. The membrane-ass
ociated form of Vif is a peripheral membrane protein which is tightly
associated with the cytoplasmic side of cellular membranes. The C term
inus of Vif was required for the stable association of Vif with membra
nes. The C terminus was also essential for Vif function, suggesting th
at the association of Vif with membranes is likely to be important for
its biological activity. The highly conserved regions at residues 103
to 115 and 142 to 150 were important for Vif function but did not aff
ect membrane association, indicating that these regions are likely to
be important for other, as-yet-unknown functions.