Divergent effects of Tat and 17beta-estradiol on proteasome activity and HIV-1 replication in human astrocytes and monocytes

As AIDS is now the third leading cause of death among women ages 25-44, understanding the role that female sex hormones might play in HIV-1 infection is especially critical. Recent data from our lab shows that estrogen has complex actions on the multicatalytic proteasome, which clears oxidized and d...

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Published in:Journal of neurovirology 2006-05, Vol.12, p.81-82
Main Authors: Turchan-Cholewo, J, Keller, J N, Nath, A, Hahn, K, Wilson, ME, Smart, E J, Bruce-Keller, A J
Format: Article
Language:English
Subjects:
Human immunodeficiency virus 1
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Summary:As AIDS is now the third leading cause of death among women ages 25-44, understanding the role that female sex hormones might play in HIV-1 infection is especially critical. Recent data from our lab shows that estrogen has complex actions on the multicatalytic proteasome, which clears oxidized and damaged proteins from cells and has been shown to be an important aspect of cellular responses to viral infection. Indeed, the proteasome is critically important to nearly all steps of the HIV viral life cycle, and can regulate HIV-1 replication. To determine how the proteasome might regulate HIV replication in the brain, we measured the effects of the HIV-1 viral protein Tat on proteasome activity in human monocytes and astrocytes. Specifically, we examined the dose (50-200 nM)-and time-dependent (6-48 h) effects of Tat1-72, Tat1-86 and Tat 1-101 and mutant Tatd31-61 on proteasome activity in monocytic THP1 cells, astrocytic SVGA cells, and primary human astrocytes. Data indicate that Tat1-72, Tat1-86, and Tat 1-101, but not Tatd31-61, significantly decreased proteasome activity in astrocytes but not THP1 cells. Proteasome activity in astrocytes was not decreased by inhibitors of lysosomal proteolysis (NH4Cl; 1 mM) or by treatment with 1 nM 17beta-estradiol. To next determine the effects of estrogen and proteasome inhibition on HIV-1 replication, we measured HIV-1 infection in human SVGA and THP-1 cells under conditions of estrogen treatment or proteasome inhibition. Interestingly, 17beta-estradiol significantly attenuated HIV infection (H9/HIV-1 IIIB) in SVGA cells, but was not effective against HIV-1 IIIB infection in THP-1 cells. Taken together, these data clearly indicate that the effects of Tat and host factors, including 17beta-estradiol, on HIV-1 regulation are cell type-specific, and further suggest that estrogens could act to attenuate HIV-1 replication in astrocytes.
ISSN:1355-0284