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95 Modulation of Host Gene Expression by Virions Bearing Host-Derived CD86 (B7-2) Molecules
M. J. Tremblay1, S. Bounou1, D. D. Richman2,3, and J. Corbeil*2,3
1Univ. Laval, Québec, Canada; 2Univ. of California, San Diego, CA, USA; and 3San Diego Veterans Med. Res. Fndn., CA, USA
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 ( 106 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.
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