Expression and Activation of a C-Terminal Truncated Isoform of STAT5 (STAT5Δ) Following Interleukin 2 Administration or AZT Monotherapy in HIV-Infected Individuals

The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

“…One group found that the levels of Stat5a, Stat5b, and Stat1 were all decreased in puri®ed T cells isolated from HIV patients, suggesting that the reduction of these STAT proteins may contribute to the loss of T cell function over the course of HIV infection (Pericle et al, 1998). In contrast, an independent study showed that the C-terminal truncated Stat5 and Stat1a were constitutively activated in peripheral blood mononuclear cells isolated from HIV patients (Bovolenta et al, 1999). The discrepancies between these two studies remain to be clari®ed.…”

HIV-Tat promotes cellular proliferation and inhibits NGF-induced differentiation through mechanisms involving Id1 regulation

“…Tyrosine phosphorylation and subsequent SH2-domain-mediated homo-or heterodimerization of Stats are essential for translocation to the nucleus and the activation of transcription. Dysregulation of Stat pathways has been shown to contribute to cancer (Bowman et al, 2000) and virally induced disease in human (Bovolenta et al, 1999(Bovolenta et al, , 2002Nguyen et al, 2002) including HIV-1 infection (Bovolenta et al, 1999).…”

Retroviral Interference on STAT Activation in Individuals Coinfected with Human T Cell Leukemia Virus Type 2 and HIV-1

“…This observation indicates that the factor(s) leading to both cleavage and preferential activation of STAT5 is present in vivo and is lost by PBMC isolation. We previously published that an increased activation of STAT5⌬ was observed in PBMC derived from HIV-1-infected subjects enrolled in a phase II clinical trial who received intermittent IL-2 administration, but not in normal PBMC infected in vitro with HIV-1 and subsequently stimulated with IL-2 (27). Because these factors are absent in both HTLV-2 and HTLV-2/HIV-1 coinfected individuals, it is tempting to speculate that this may be a direct reflection of the higher pathogenic potential of HIV-1 vs HTLV-2, but also highlights a sort of dominance of HTLV-2 over HIV-1 in terms of maintaining T cells in a primed but not absolutely activated STAT5⌬ activated state.…”

“…In addition, we have recently shown that most (75%) HIV-1 seropositive patients display a constitutive activation of STAT5⌬ and STAT1 in their freshly isolated and unstimulated PBMC (26). Interestingly, this abnormality was transiently suppressed by zidovudine monotherapy (27). However, no information on the activation state of STATs in HTLV-2-infected individuals is currently available.…”