Expression and activation of a C-terminal truncated isoform of STAT5 (STAT5 Delta) following interleukin 2 administration or AZT monotherapy in HIV-infected individuals.
Intermittent administration of recombinant interleukin-2 (rIL-2) to individuals infected with human immunodeficiency virus (HIV) has been shown to raise and maintain the absolute number of circulating CD4(+) T cells to normal or near normal levels. One of the signaling pathways triggered by IL-2 is the Janus kinase-signal transducer and activator of transcription (JAK-STAT). In particular, IL-2 activates the tyrosine kinases JAK1 and JAK3 and the transcription factors STAT3 and STAT5. We have previously observed that most HIV(+) individuals, unlike healthy seronegative controls, show a constitutive activation of STAT1 and a C-terminal truncated isoform of STAT5 (STAT5 Delta). In the present study, we have analyzed the protein level and activation state of STAT5 isoforms expressed in peripheral blood mononuclear cells of two HIV-infected individuals who showed a good or a poor response to intermittent IL-2 administration, respectively, and of a single individual before and after initiation of Zidovudine monotherapy. We provide evidence that both therapeutic interventions enhanced the expression and activation of the C-terminal truncated isoform of STAT5 (STAT5 Delta) in vivo.
Bovolenta
C
C
AIDS Immunopathogenesis Unit, DIBIT, 20132 Milano, Italy.
Camorali
L
L
Mauri
M
M
Ghezzi
S
S
Nozza
S
S
Tambussi
G
G
Lazzarin
A
A
Poli
G
G
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008894:Milk Proteins; D020033:Protein Isoforms / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D008894:Milk Proteins; D020033:Protein Isoforms; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D015215:Zidovudine; D004247:DNA