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

被引:45
作者
Bencheikh, M [1 ]
Bentsman, G [1 ]
Sarkissian, N [1 ]
Canki, M [1 ]
Volsky, DJ [1 ]
机构
[1] Columbia Univ, St Lukes Roosevelt Hosp Ctr, Mol Virol Lab, New York, NY USA
关键词
HIV-1; tropism; DNA transfection; neuropathogenesis; AIDS;
D O I
10.3109/13550289909021993
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Dementia is a common complication of AIDS which is associated with human immunodeficiency virus type 1 (HIV-1) infection of brain macrophages and microglia. Recent studies have shown that astrocytes are also infected in the brain but HIV-1 replication in these cells is restricted. To determine Virus specificity of this restriction we tested the expression of 15 HIV-1 molecular clones in primary human fetal astrocytes by infection and DNA transfection. Infection with cell-free viruses was poorly productive and revealed no clone-specific differences. In contrast, transfected cells produced transiently high levels of HIV-1 p24 core antigen, up to 50 nanograms per mi culture 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 the differences and the subsequent virus spread did not correlate with the tropism 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 expression and promoted maintenance of HIV-1 infection. We conclude that primary astrocytes present no fundamental barriers to moderate expression of different strains of HIV-1 and that the presence of functional Nef is advantageous to virus infection in these cells.
引用
收藏
页码:115 / 124
页数:10
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