HIV-1 NL4-3, but not IIIB, inhibits JAK3/STAT5 activation in CD4(+) T cells.
HIV-1 infection leads to T cell dysfunction and apoptosis in vivo and in vitro. The shared common gamma chain of IL-2R and its associated Janus kinase, JAK3, are indispensable for normal T cell function and survival. We have reported that CD4 ligation with HIV gp120 inhibits T cell receptor-induced activation and expression of JAK3. We have also shown that while some strains of HIV-1, such as NL4-3, induce apoptosis of infected CD4(+) T cells, other strains, such as HIV-1 IIIB, do not. Interestingly, we show here that infection of CD4(+) T cells with HIV-1 NL4-3, but not IIIB, inhibited activation and expression of JAK3. NL4-3-infected T cells were unable to upregulate JAK3 expression following stimulation through TCR/CD3. In addition, NL4-3, but not IIIB, inhibited tyrosine phosphorylation and expression of STAT5, a downstream target of JAK3. These data suggest a correlation between apoptosis of HIV-1-infected T cells and inhibition of the JAK3/STAT5 activation pathway.
Selliah
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Division of Rheumatology, The Children's Hospital of Philadelphia, 3516 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA.
Finkel
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TH
D017209:Apoptosis; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015497:HIV-1 / Q000145:classification / Q000472:pathogenicity*; D006801:Humans; D053616:Janus Kinase 3; D008213:Lymphocyte Activation; D008894:Milk Proteins; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*
D017252:CD3 Complex; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3