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

J Neurovirol. 1999 Apr;5(2):115-24. doi: 10.3109/13550289909021993.

Abstract

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 ml 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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Astrocytes / virology*
  • Cell Culture Techniques
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique, Indirect
  • Genes, nef / physiology*
  • HIV Core Protein p24 / analysis
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • HIV-1 / physiology*
  • Humans
  • Sensitivity and Specificity
  • Time Factors
  • Transfection
  • Virus Replication / physiology

Substances

  • HIV Core Protein p24