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

Abstract

Human T cell leukemia virus (HTLV) type-2 is a human retrovirus whose infection has not been tightly linked to human diseases. However, the fairly high prevalence of this infection among HIV-1-positive individuals indicates the importance of better understanding the potential interference of HTLV-2 infection on HIV-1 infection and AIDS. We previously demonstrated that one signature of PBMC freshly derived from HIV-1-infected individuals is the constitutive activation of a C-terminal truncated STAT5 (STAT5Δ). Therefore, we analyzed the potential activation of STATs in HTLV-2 monoinfected and HTLV-2/HIV-1 dually infected individuals. We observed that PBMC of HTLV-2-infected individuals do not show STAT activation unless they are cultivated ex vivo, in the absence of any mitogenic stimuli, for at least 8 h. The emergence of STAT activation, namely of STAT1, in culture was mostly related to the secretion of IFN-γ. Of note, this phenomenon is not only a characteristic feature of HTLV-2-infected individuals but also occurred with PBMC of HIV-1+ individuals. Surprisingly, HTLV-2/HIV-1 coinfection resulted in low/absent STAT activation in vivo that paralleled a diminished secretion of IFN-γ after ex vivo cultivation. Our findings indicate that both HTLV-2 and HIV-1 infection prime T lymphocytes for STAT1 activation, but they also highlight an interference exerted by HTLV-2 on HIV-1-induced STAT1 activation. Although the nature of such a phenomenon is unclear at the present, these findings support the hypothesis that HTLV-2 may interfere with HIV-1 infection at multiple levels.

The F12-Vif derivative Chim3 inhibits HIV-1 replication in CD4+ T lymphocytes and CD34+-derived macrophages by blocking HIV-1 DNA integration

“…29 Western blot analysis was performed as in Vallanti et al 5 HIV-1 HXB2 Vif rabbit antiserum 30 Coimmunoprecipitations were performed as follows: HEK-293T cells were cotransfected with the Vifs-tag vectors in the possible combinations to determine both the WT-Vif and Chim3 homodimers and WT-Vif/Chim3 heterodimer. After 36 hours, cells were lysed in the lysing buffer (150 mM NaCl, 50 mM Tris-HCl, pH 7.5, 0.5% NP-40, and a cocktail of protease inhibitors).…”

Postgenomic up-regulation of CCL3L1 expression in HTLV-2–infected persons curtails HIV-1 replication

“…[20][21][22] Both anti-inflammatory cytokines and IFNs can suppress both transcriptional and posttranscriptional steps in the HIV life cycle. 23 Of interest, putative regulatory sequences of CCL3 and CCL3L1 genes have been detected in the promoter regions of human GMCSF and IFNG, 24 which code for 2 cytokines that can strongly modulate the susceptibility of macrophages to HIV-1 infection.…”

Preexisting Infection with Human T-Cell Lymphotropic Virus Type 2 neither Exacerbates nor Attenuates Simian Immunodeficiency Virus SIV mac251 Infection in Macaques

“…Coinfection with HTLV-2 did not affect the level of SIV mac251 RNA or DNA in plasma or tissues. HTLV-2 infection has been demonstrated to affect the activation of signal transducers and activators of transcription (STAT) genes in HTLV-2/HIV-1 coinfected patients (10), and the IFN-␥ gene promoter can be activated by the HTLV-2 trans-activator Tax protein (11). However, unlike HTLV-1 (41), HTLV-2 does not induce constitutive STAT-5 activation (42).…”