Replication of different clones of human immunodeficiency virus type 1 in primary fetal human astroyctes: enhancement of viral gene expression by Nef

Dementia is a common complication of AIDS which is associated with human im munodeficiency virus type 1 (HIV-1) infection of brain macrophages and micr oglia. Recent studies have shown that astrocytes are also infected in the b rain but HIV-1 replication in these cells is restricted. To determine Virus specificity of this restriction we tested the expression of 15 HIV-1 molec ular clones in primary human fetal astrocytes by infection and DNA transfec tion. Infection with cell-free viruses was poorly productive and revealed n o clone-specific differences. In contrast, transfected cells produced trans iently high levels of HIV-1 p24 core antigen, up to 50 nanograms per mi cul ture supernatant, and nanogram levels of p24 were detected 3-4 weeks after transfection of some viral clones. The average peak expression of HIV-1 in astrocytes varied as a function of viral clone used by a factor of 15 but t he differences and the subsequent virus spread did not correlate with the t ropism of the viral clones to T cells or macrophages. Functional vif, vpu, and vpr genes were dispensable for virus replication from transfected DNA, but intact nef provided a detectable enhancement of early viral gene expres sion and promoted maintenance of HIV-1 infection. We conclude that primary astrocytes present no fundamental barriers to moderate expression of differ ent strains of HIV-1 and that the presence of functional Nef is advantageou s to virus infection in these cells.