Interferon α and Tat involvement in the immunosuppression of uninfected T cells and C-C chemokine decline in AIDS

Zagury, Daniel; Lachgar, A; Chams, Vida; Fall, Lat S.; Bernard, Jacky; Zagury, Jean François; Bizzini, B; Gringeri, A.; Santagostino, Elena; Rappaport, Jay; Feldman, Michaël; Burny, Arsène; Gallo, Robert C.

doi:10.1073/pnas.95.7.3851

Cited by 162 publications

(118 citation statements)

References 42 publications

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“…High levels of TdRev expression in target cells require transactivation of the LTR by Tat, a protein that has been implicated in causing apoptosis and immunosuppression of uninfected T cells. [45][46][47] Deletion of the second exon of Tat which mediates its binding to cellular integrins would prevent effects on bystander cells while still being able to carry out full transactivation of the LTR promoter. Additionally, deletion of env coding sequences from pTRG would avoid the toxic effects associated with env expression.…”

Section: Figure 9 Infectivity Of Virions Released From Supt1/trg and mentioning

confidence: 99%

Inhibition of HIV-1 replication by novel lentiviral vectors expressing transdominant Rev and HIV-1 env antisense

2002

Gene Ther

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Section: Figure 9 Infectivity Of Virions Released From Supt1/trg and mentioning

confidence: 99%

Inhibition of HIV-1 replication by novel lentiviral vectors expressing transdominant Rev and HIV-1 env antisense

2002

Gene Ther

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“…Specifically, antibody (Ab) responses to Tat have been associated with non-progression to AIDS [23][24][25][26][27][28]. Similarly, anti-Tat CTLs have been shown to inversely correlate with progression to AIDS [29,30].…”

Section: Introductionmentioning

confidence: 99%

Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys

Maggiorella

Baroncelli

Michelini

et al. 2004

Vaccine

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Vaccination with a biologically active Tat protein or tat DNA contained infection with the highly pathogenic SHIV89.6P virus, preventing CD4 T-cell decline and disease onset. Here we show that protection was prolonged, since neither CD4 T-cell decline nor active virus replication was observed in all vaccinated animals that controlled virus replication up to week 104 after the challenge. In contrast, virus persisted and replicated in peripheral blood mononuclear cells and lymph nodes of infected animals, two of which died. Tat-specific antibody, CD4 and CD8 T-cell responses were high and stable only in the animals controlling the infection. In contrast, Gag-specific antibody production and CD4 and CD8 T-cell responses were consistently and persistently positive only in the monkeys that did not control primary virus replication. These results indicate that vaccination with Tat protein or DNA induced long-term memory Tat-specific immune responses and controlled primary infection at its early stages allowing a long-term containment of virus replication and spread in blood and tissues.

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“…Thus, Tat has been involved in both apoptotic (4 -6) and survival (7,8) mechanisms in the alteration of T cell proliferation (9) and in the aberrant expression of several cytokine genes: TNF-␣ (10), TGF-␤ (11), IL-6 (12), IL-2 (13-16), IFN-␣ (17), and IL-8 (18). Many of these effects are thought to be mediated by alterations of cellular gene expression by Tat.…”

mentioning

confidence: 99%

HIV-1 Tat Inhibits IL-2 Gene Transcription Through Qualitative and Quantitative Alterations of the Cooperative Rel/AP1 Complex Bound to the CD28RE/AP1 Composite Element of the IL-2 Promoter

González

Punzón

González

et al. 2001

The Journal of Immunology

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Dysregulation of cytokine secretion plays an important role in AIDS pathogenesis. Here, we demonstrate that expression of HIV-1 Tat protein in Jurkat cells induces a severe impairment of IL-2 but not TNF gene transcription. Interestingly, this inhibition correlates with the effect of the viral protein on the transactivation of the CD28RE/AP1 composite element (−164/−154), but not with that observed on the NFAT/AP1 site of the IL-2 gene promoter, neither with the effect on NF-κB- nor AP1-independent binding sites. Endogenous expression of Tat induced a decrease in the amount of the specific protein complex bound to the CD28RE/AP1 probe after PMA plus calcium ionophore stimulation. This effect was accompanied by qualitative alterations of the AP1 complex. Thus, in wild-type Jurkat cells, c-jun was absent from the complex, whereas in Tat-expressing cells, c-jun was increasingly recruited overtime. By contrast, similar amounts of c-rel and a small amount of NFAT1 were detected both in wild type and in Jurkat Tat+ cells. Furthermore, Tat not only induced the participation of c-jun in the cooperative complex but also a decrease in its transactivation activity alone or in combination with c-rel. Thus, the interaction of Tat with the components of this rel/AP1 cooperative complex seems to induce quantitative and qualitative alterations of this complex as activation progresses, resulting in a decrease of IL-2 gene transcription. Altogether our results suggest the existence of tuned mechanisms that allow the viral protein to specifically affect cooperative interactions between transcription factors.

show abstract

Interferon α and Tat involvement in the immunosuppression of uninfected T cells and C-C chemokine decline in AIDS

Cited by 162 publications

References 42 publications

Inhibition of HIV-1 replication by novel lentiviral vectors expressing transdominant Rev and HIV-1 env antisense

Inhibition of HIV-1 replication by novel lentiviral vectors expressing transdominant Rev and HIV-1 env antisense

Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys

HIV-1 Tat Inhibits IL-2 Gene Transcription Through Qualitative and Quantitative Alterations of the Cooperative Rel/AP1 Complex Bound to the CD28RE/AP1 Composite Element of the IL-2 Promoter

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