Host and virus strain dependence in activation of human macrophages by human immunodeficiency virus type 1.
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.
Kazmierczak
Katarzyna
K
Molecular Virology Division, St. Luke's-Roosevelt Hospital Center, Columbia University Medical Center, 432 West 58th Street, New York, NY 10019, USA.
Potash
Mary Jane
MJ
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000503:physiopathology / Q000821:virology; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000145:classification / Q000502:physiology*; D006801:Humans; D007378:Interleukins / Q000235:genetics; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000821:virology*
D007378:Interleukins