Varin A, Decrion AZ, Roques BP, Aggarwal BB, Herbein G; IAS Conference on HIV Pathogenesis and Treatment (2nd : 2003 : Paris, France).

Antivir Ther. 2003; 8 (Suppl.1): abstract no. 327.

Department of Virology and Institut d'Etude et de Tansfert de Genes, Franche-Comte University - F25030 Besancon, France

The HIV-1 Vpr accessory gene product is a 14 kDa virion-associated protein, which is involved in cell cycle and apoptosis control, nuclear import of preintegration complexes and transactivation of cellular and viral promoters. Most of the data obtained so far have been in experiments with endogenous Vpr protein, so far overlooking the effects of exogenous soluble Vpr protein. Using synthetic Vpr protein, we studied the activation of nuclear transcription factors NF-kappaB, AP-1 and JNK by EMSA in the promonocytic cell line U937 and in the lymphoid cell line Jurkat. Exogenous Vpr activated NF-kappaB and AP-1 in a dose- and time-dependent manner in both cell lines. The stimulation of NF-kappaB and AP-1 by exogenous Vpr was specific since it was totally inhibited by treatment with a neutralizing anti-Vpr antibody. Since exogenous Vpr activated NF-kappaB and AP-1, which bind to the HIV-1 long terminal repeat (LTR), we investigated the effect of exogenous Vpr on HIV-1 transcription. Exogenous Vpr stimulated the HIV-1 LTR via NF-kappaB activation in U937 cells and in Jurkat cells, and enhanced viral replication in the chronically infected monocytic and lymphoid cells U1 and ACH2, respectively. Overall our results suggest a critical role for exogenous Vpr in AIDS pathogenesis via stimulation of HIV-1 provirus present in cellular reservoirs.

Publication Types:

• Meeting Abstracts

Keywords:

• Acquired Immunodeficiency Syndrome
• Cell Line
• Gene Products, vpr
• Genes, vpr
• HIV Long Terminal Repeat
• HIV-1
• Humans
• Jurkat Cells
• Monocytes
• NF-kappa B
• Proviruses
• Trans-Activation (Genetics)
• Transcription Factor AP-1
• Transcription Factor RelA
• Transcription Factors
• Transcription, Genetic
• U937 Cells
• Virion
• genetics

Other ID:

• GWAIDS0022988

UI: 102262612

From Meeting Abstracts