Abstract
Human immunodeficiency virus type 1 (HIV-1)–associated neuropathogenesis occurs in a large minority of infected people. Presently, there are neither viral nor cellular markers that predict the development of brain disease during HIV-1 infection. This study was conducted to determine whether there exist systematic differences among human cell donors and virus strains for the activation of macrophage gene expression by HIV-1 that may contribute to neuropathogenesis. Four HIV-1, ADA and B-aL, which were isolated from peripheral tissues of acquired immunodeficiency syndrome (AIDS) patients, and DJV and YU-2, which were isolated from brains of patients with HIV-1–associated dementia, were compared for induction of expression of cellular genes associated with antiviral activity or inflammation in monocyte-derived macrophages from several donors. Virus replication and cytokine production were scored by enzyme-linked immunosorbent assay (ELISA) and cellular transcripts were measured by real-time polymerase chain reaction (PCR). ADA and B-aL productively infected cells from all donors tested and induced all cellular transcripts tested, illustrating a common response of macrophages to HIV-1 replication. In sharp contrast, the viruses associated with neuropathogenesis, DJV and YU-2, induced intense gene expression early after infection in cells from a subset of donors but DJV did not productively infect these cells. No such heterogeneity was observed in the responses of macrophages during high-level replication of any HIV-1 tested. The susceptibility to early activation by HIV-1 may reflect susceptibility to neuropathogenesis in AIDS.
The authors thank the members of the Molecular Virology Division for stimulating discussions, Dr. G. Bentsman for expert assistance, and Ms. I. M. Totillo for manuscript preparation. This work was supported by PHS grants NS39191 and NS43110.