Sheeter DA, Leoni LM, Genini D, Carson DA, Richman DD, Corbeil J; Conference on Retroviruses and Opportunistic Infections.

Program Abstr 6th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 6th 1999 Chic Ill. 1999 Jan 31-Feb 4; 6th: 128 (abstract no. 316).

University of California, San Diego.

Replication of HIV-1 in human T lymphocytes requires the activation of host cellular proteins. This study determined that ATF-2 is upregulated in HIV infection despite the blockade of the upstream p38 kinase. CEM-GFP, a reporter lymphoblastoid T-cell line was pre-incubated with the specific p38 kinase inhibitor SB203580 at 10 uM and subsequently infected with HIV-1. At high multiplicity of infection (MOI: 0.1), HIV replication was not affected by p38 blockade and no significant differences in apoptosis, HIV replication, or in the proportion of ATF-2 phosphorylation was observed. However, at lower MOI (0.001), where presumably modest initial differences in the proportion of infected cells can be amplified over time, we found that ATF-2 phosphorylation was increased. Pre-treatment with SB203580 blocked this ATF-2 phosphorylation and protected the infected cells by reducing the percentage of infected and apoptotic cells as well as reducing the p24 antigen output. Interestingly, the ATF-2 phosphorylation correlated with the percentage of cells present in the G2/M phase of the cell cycle. These results indicate that ATF-2 phosphorylation occurs independently of p38 kinase activity and that ATF-2 activation may be a relevant cellular event that contributes to HIV-1 infection and pathogenesis.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Activating Transcription Factor 2
• Apoptosis
• Cell Cycle
• Cell Division
• HIV-1
• Humans
• Mitogen-Activated Protein Kinase 14
• Mitosis
• Phosphorylation
• Pyridines
• SB 203580
• T-Lymphocytes
• genetics

Other ID:

• 20711558

UI: 102188971

From Meeting Abstracts