HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VPU HAS A CD4-GLYCOPROTEIN AND ANENVELOPE GLYCOPROTEIN-INDEPENDENT FUNCTION

Vpu is a 16-kDa membrane-associated phosphoprotein that is expressed f rom the same, singly spliced message as the human immunodeficiency vir us type 1 (HIV-1) envelope glycoprotein precursor, gp160. Previous stu dies suggest that Vpu functions in the late stages of viral replicatio n, possibly in virus egression from the cell. Recently, it has been de monstrated that Vpu functions to allow gp160 to be more efficiently pr ocessed by disrupting CD4-gp160 complexes generated by transfection of HeLa cells. We show here that the lack of expression of intact Vpu re sults in a 90% reduction in infectious virus produced over a single ro und of replication from HeLa cells in the absence of CD4 expression. T his reduction persists when HIV-1 particles are pseudotyped with the H IV-2 or amphotropic murine leukemia virus envelope glycoprotein. Pulse -chase analysis of HIV-1 capsid protein (p24) in the absence of CD4 an d envelope glycoprotein demonstrates that the rate of virus release is reduced when Vpu is not expressed. Our findings indicate that Vpu has a function involving particle release not dependent on CD4 or envelop e glycoprotein expression.