Human immunodeficiency virus type 1 infection alters chemokine β peptide expression in human monocytes: Implications for recruitment of leukocytes into brain and lymph nodes

Two chemokine (chemoattractant cytokines) β peptides, macrophage inflammatory proteins 1α and 1β (MIP-1α and MIP-1β), were induced in human monocyte cultures following infection with the human immunodeficiency virus type 1 (HIV-1). Induction depended on productive viral infection: not only did the kinetics of MIP-1 peptide induction closely follow those of viral replication, but monocyte cultures inoculated with heat-inactivated virus or infected in the presence of AZT failed to produce these chemokine β peptides. In addition, HIV infection markedly altered the pattern of β chemokine expression elicited by tumor necrosis factor (TNF), itself a potent proinflammatory cytokine up-regulated during the development of AIDS. Reverse transcription (RT)-PCR and RT-in situ PCR studies on brain tissue from patients with AIDS dementia demonstrated elevated MIP-1α and MIP-1β mRNA expression relative to comparable samples from HIV-1-infected patients without dementia. Cells expressing chemokines in HIV-1-infected brains were identified morphologically as microglia and astrocytes. As MIP-1α and MIP- 1β are potent chemoattractants for both monocytes and specific subpopulations of lymphocytes, this dysregulation of β chemokine expression may influence the trafficking of leukocytes during HIV infection. These data, taken together, suggest a mechanism by which HIV-1-infected monocytes might recruit uninfected T cells and monocytes to sites of active viral replication or inflammation, notably the brain and lymph nodes.