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AIDS. 2001 Mar 9;15(4):433-40.

The HIV-1 transactivator protein Tat is a potent inducer of the human DNA repair enzyme beta-polymerase.

Author information

1
Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.

Abstract

OBJECTIVE:

This study examines the effects of the HIV-1 regulatory proteins, Tat and Rev, on the expression of the DNA polymerase beta (beta-pol) gene, which encodes a key protein in the DNA base-excision repair pathway. The rationale for these experiments is to examine the potential involvement of base-excision repair protein deregulation in HIV-1-related lymphomas.

DESIGN:

Expression of beta-pol mRNA was examined in AIDS-related lymphomas and non-AIDS-related lymphomas and as a function of HIV-1 infection of B cells in culture. The effect of Tat or Rev over-expression on beta-pol promoter expression was tested by transient co-transfection assays with a beta-pol promoter reporter plasmid and a Tat or Rev over-expression plasmid.

METHODS:

Northern blot analysis was used to quantitate beta-pol expression in lymphoma and cells. Raji cells were co-transfected with a chloramphenicol acetyltransferase (CAT) reporter plasmid and a plasmid over-expressing Tat or Rev. CAT activity was measured in transfected cells.

RESULTS:

beta-Pol mRNA was > 10-fold higher in AIDS-related than in non-AIDS B-lineage lymphomas. beta-Pol expression was up-regulated in a B-cell line upon infection with HIV-1, and increased in Raji cells upon recombinant expression of the Tat gene. The beta-pol promoter was transactivated (fourfold induction) by Tat, but not by Rev. Tat-dependent transactivation required a binding site for the transcription factor Sp1 in the beta-pol promoter.

CONCLUSION:

These results suggest that HIV-1 Tat can interact with cellular transcription factors to increase the steady-state level of beta-pol in B cells. Tat-mediated induction of beta-pol may alter DNA stability in AIDS-related lymphomas.

[Indexed for MEDLINE]

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