Tremblay MJ, Bounou S, Richman DD, Corbeil J.
AIDS Vaccine 2001. 2001 Sep 5-8; abstract no. 95.
Univ. Laval, Qubec, Canada
BACKGROUND: We investigated the modulation of gene expression in Jurkat cells when CD86, a host-encoded molecule, was present or absent from the surface of virions. Our aim is to investigate the role of CD86 in HIV infectivity and pathogenesis.METHODS: Isogenic viruses (NL4-3 backbone) were generated in 293T cells with or without CD86 on their surface. 5 ( 10[6] Jurkat cells were infected with 106 pg (p24 equivalence) of CD86-bearing viruses and the control viruses without CD86. Aliquots of cultured cells were taken at 2, 4, 8, 12, and 24 h during the course of infection and analyzed for gene expression with the Affymetrix U95A Genechip. This chips interrogates 12,000 known genes.RESULTS: Many host genes were modulated differentially when comparing infection with viruses with or without CD86. The presence of CD86 induced the expression of interleukin 7 and SDF-1 at all time points following infection. CD86 also up-regulated jun kinase 2 (JNK2) starting 8 h after infection. JNK2 phosphorylates ATF-2, which increases transcription from the HIV-1 LTR. This suggests the activation of the Ras /MAPK pathway. Complementing this hypothesis, RAS suppressor protein 1 (L12535) was found to be down-regulated at all time points in the context of CD86-bearing virions.CONCLUSIONS: This approach can be used to investigate any surface components of HIV-1 for infectivity and pathogenesis. It has broad utility in identifying important modulators of HIV functions and may be useful in vaccine development.
Publication Types:
Keywords:
- Activating Transcription Factor 2
- Antigens, CD
- Antigens, CD80
- CD86 protein, human
- HIV Infections
- HIV Long Terminal Repeat
- HIV-1
- Humans
- Jurkat Cells
- Membrane Glycoproteins
- RSU1 protein, human
- Transcription Factors
- Transcription, Genetic
- Virion
- genetics
- immunology
Other ID:
UI: 102249203
From Meeting Abstracts