HIV-1 infection and regulation of Tat function in macrophages

The macrophage is an important cell type in the pathophysiology of human immunodeficiency virus type I (HIV-1) infection. Macrophages both support viral replication and are capable of attracting and activating lymphocytes, thus rendering CD4(+) T lymphocytes highly permissive for infection. The viral Tat protein, whose function is mediated by the cellular cyclin T I protein complexed with CDK9, is required for efficient transcription of the integrated HIV-1 provirus by RNA polymerase II. Cyclin T1 expression is highly regulated during macrophage differentiation, and this has important implications for HIV-1 replication. In monocytes isolated from healthy blood donors, cyclin T1 protein expression is low and is induced to high levels within the first few days of differentiation by a post-transcriptional mechanism. After 1-2 weeks of macrophage differentiation, however, cyclin T1 expression is shut off. Treatment of macrophages with lipopolysaccharide (LPS) can re-induce cyclin T1, indicating that the activation status of macrophages can regulate cyclin T1 expression. Recent results indicate that HIV-1 infection is able to induce cyclin T1 expression in macrophages. Future studies of cyclin T1 regulation in macrophages may suggest means of manipulating expression of this crucial cellular co-factor for therapeutic benefit in HIV-1 infected individuals. (C) 2004 Elsevier Ltd. All rights reserved.