Retroviral interference on STAT activation in individuals coinfected with human T cell leukemia virus type 2 and HIV-1.
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 (STAT5Delta). 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-gamma. 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-gamma 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.
Bovolenta
Chiara
C
Department of Immunology and Infectious Disease, San Raffaele Scientific Institute, via Olgettina 58, 20132 Milan, Italy. c.bovolenta@hsr.it
Pilotti
Elisabetta
E
Mauri
Massimiliano
M
Panzeri
Barbara
B
Sassi
Monica
M
Dall'Aglio
PierPaolo
P
Bertazzoni
Umberto
U
Poli
Guido
G
Casoli
Claudio
C
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D015491:HTLV-II Infections / Q000150:complications / Q000276:immunology* / Q000821:virology*; D015367:Human T-lymphotropic virus 2 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008894:Milk Proteins; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D015534:Trans-Activators / Q000378:metabolism; D014762:Viral Interference / Q000276:immunology*
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D007371:Interferon-gamma