Herbein G, Varin A, Decrion AZ, Roques BP, Aggarwal BB; International Conference on AIDS (15th : 2004 : Bangkok, Thailand).

Int Conf AIDS. 2004 Jul 11-16; 15: abstract no. MoPeA3053.

Department of Virology Franche-Comte University, Besancon, France

Background: The HIV-1 Vpr gene product is a 14 kDa virion-associated protein which is involved in cell cycle and apoptosis control, nuclear import of pre-integration complexes and transactivation of cellular and viral promoters. Most of the data obtained so far have been reported in experiments with endogenous Vpr protein but exogenous Vpr protein is detected in the serum of HIV-1 infected subjects and might play a role in HIV pathogenesis. Methods: Using exogenous Vpr protein, we studied the activation of nuclear transcription factors NFkB, AP-1 and JNK by EMSA in primary macrophages. We also determined the effect of exogenous Vpr protein on HIV-1 replication in primary macrophages. Results: Exogenous Vpr activated NFkB and AP-1 in a dose- and time- dependent manner in primary macrophages. Activation of JNK is an early event initiated by many stress stimuli and is required for AP-1 activation. The N-terminus of exogenous Vpr activated JNK in a time-dependent manner in primary macrophages. Since exogenous Vpr activated NFkB 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 in primary macrophages. The N-terminus of exogenous Vpr enhanced HIV-1 replication in primary macrophages. Conclusion Our results indicate that exogenous Vpr protein activates HIV-1 replication in primary macrophages and therefore might be a new target for therapy.

Publication Types:

• Meeting Abstracts

Keywords:

• Acquired Immunodeficiency Syndrome
• Active Transport, Cell Nucleus
• Anti-HIV Agents
• Gene Products, vpr
• Genes, vpr
• HIV
• HIV Infections
• HIV Long Terminal Repeat
• HIV-1
• Macrophages
• NF-kappa B
• Promoter Regions (Genetics)
• Trans-Activation (Genetics)
• Transcription Factor AP-1
• Virion
• genetics

Other ID:

• GWAIDS0035143

UI: 102279359

From Meeting Abstracts