CD28-dependent HIV-1 transcription is associated with Vav, Rac, and NF-kappa B activation.
Activation of HIV-1-infected T cells through the T cell receptor and costimulatory molecule CD28 induces proviral transcription; however, the mechanism behind this enhanced virus expression is unknown. Jurkat T cells and primary CD4+ T cells expressing a CD8 alpha/CD28 chimeric receptor containing a mutation at tyrosine 200 in the cytoplasmic tail were unable to fully induce HIV-1 proviral transcription in response to CD8 alpha/28 receptor cross-linking in comparison to CD28 costimulation. The loss of transactivation seen with the mutant chimeric receptor correlated with a decrease in Vav tyrosine phosphorylation. CD28-dependent activation of HIV-1 transcription also required the GTPase activity of Rac1, which was not activated during costimulation with the mutated receptor. Furthermore, the mutated receptor was unable to induce NF-kappa B DNA binding or transactivation, as demonstrated by electromobility shift assays and HIV-1 long terminal repeat and NF-kappa B-dependent reporter constructs. These studies show that signaling events initiated by tyrosine 200 of CD28 are required for efficient expression of HIV-1 transcription in activated T cells.
Cook
Julie A
JA
Graduate Program in Biochemistry, Microbiology, and Molecular Biology, the Department of Biochemistry, Pennsylvania State University, University Park, 16802, USA.
Albacker
Lee
L
August
Avery
A
Henderson
Andrew J
AJ
D015703:Antigens, CD / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D016328:NF-kappa B / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism; D010766:Phosphorylation; D051567:Proto-Oncogene Proteins c-vav; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D014443:Tyrosine; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D015703:Antigens, CD; D018106:CD28 Antigens; D016328:NF-kappa B; D015513:Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; C496618:VAV1 protein, human; D014443:Tyrosine; D020830:rac1 GTP-Binding Protein