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-a (rIL-2) to individ uals infected with human immunodeficiency virus (HIV) has been shown to rai se 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 mo st HIV+ individuals, unlike healthy seronegative controls, show a constitut ive activation of STAT1 and a C-terminal truncated isoform of STAT5 (STAT5 Delta). In the present study, we have analyzed the protein level and activa tion state of STAT5 isoforms expressed in peripheral blood mononuclear cell s of two HIV-infected individuals who showed a good or a poor response to i ntermittent IL-2 administration, respectively, and of a single individual b efore and after initiation of Zidovudine monotherapy. We provide evidence t hat both therapeutic interventions enhanced the expression and activation o f the C-terminal truncated isoform of STAT5 (STAT5 Delta) in vivo. (C) 2001 Academic Press.