Effect of Antibody to HIV-1 Tat Protein on Viral Replication in Vitro and Progression of HIV-1 Disease in Vivo

Re, Maria Carla; Furlini, G.; Vignoli, M.; Ramazzotti, E.; Roderigo, G; Rosa, Vincenzo De; Zauli, Giorgio; Lolli, Serena; Capitani, Silvano; Plaça, M. La

doi:10.1097/00042560-199512000-00003

Cited by 103 publications

(58 citation statements)

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“…Because of the widely recognized protective effect of anti-Tat antibodies in HIV-seropositive individuals (15,(38)(39)(40)(41), our data could allow the design of vaccination strategies intended to partially reduce the negative effects of Tat on the host immune system.…”

Section: Discussionmentioning

confidence: 96%

Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4⁺T cell hyperactivation and HIV type 1 replication

Secchiero

Zella

Curreli

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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We show here that HIV type 1 (HIV-1) Tat protein, in combination with anti-CD3͞CD28 mAbs, promotes IL-2 production and proliferation of primary CD4 ؉ T lymphocytes, obtained from HIV-1-seronegative donors. This effect was observed when Tat was immobilized on a solid support, but it was not observed with soluble Tat. Such hyperactivation was accomplished by recruiting the rolipram-sensitive cyclic nucleoside phosphodiesterase 4 and resulted in increased susceptibility to HIV-1 infection. Accordingly, rolipram potently inhibited HIV-1 replication in cultures stimulated by anti-CD3͞CD28 ؎ Tat. These results add to the concept that decreasing Tat activity is an important addition to anti-HIV-1 therapy, and they suggest a target for anti-HIV-1 chemotherapy, phosphodiesterase 4.

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Section: Discussionmentioning

confidence: 96%

Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4⁺T cell hyperactivation and HIV type 1 replication

Secchiero

Zella

Curreli

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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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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“…27). In support, a limited number of epidemiological studies have documented an inverse relationship between the level of Tatspecific serum antibodies and the rate of disease progression (28)(29)(30). Also, a recent Tat vaccine study in nonhuman primates generated partial restoration of the immune response to simian͞HIV antigens after challenge (31).…”

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confidence: 96%

A Tat subunit vaccine confers protective immunity against the immune-modulating activity of the human immunodeficiency virus type-1 Tat protein in mice

Agwale

Shata²,

Reitz³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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The rational design of new therapies against HIV-1 necessitates an improved understanding of the mechanisms underlying the production of ineffective immune responses to HIV-1 in most infected individuals. This report shows that the CD8 ؉ T cell responses to gp120 were greatly diminished in mice vaccinated with a bicistronic gp120-Tat DNA vaccine, compared with those induced by a DNA vaccine encoding gp120 alone. The CD8 ؉ T cell responses induced by the latter included strong gp120-specific IFN-␥ secretion and protective antiviral immunity against challenge by a vacciniaenv pseudotype. The degree to which Tat influenced CD8 ؉ T cell responses depended on the bioactivity of Tat. Thus, a bicistronic DNA vaccine that expresses gp120 and a truncated Tat defective for LTR activation elicited strong IFN-␥ -secreting CD8 ؉ T cell responses to gp120 but conferred only marginal protection against the vaccinia-env challenge. The effect of Tat was completely blocked, however, by immunization with inactivated Tat protein before vaccination with the bicistronic gp120-Tat DNA vaccine.HIV-1 ͉ immune response ͉ CD8 ϩ T cell ͉ regulation

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Effect of Antibody to HIV-1 Tat Protein on Viral Replication in Vitro and Progression of HIV-1 Disease in Vivo

Cited by 103 publications

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Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4⁺T cell hyperactivation and HIV type 1 replication

Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4⁺T cell hyperactivation and HIV type 1 replication

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

A Tat subunit vaccine confers protective immunity against the immune-modulating activity of the human immunodeficiency virus type-1 Tat protein in mice

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Effect of Antibody to HIV-1 Tat Protein on Viral Replication in Vitro and Progression of HIV-1 Disease in Vivo

Cited by 103 publications

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Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+T cell hyperactivation and HIV type 1 replication

Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+T cell hyperactivation and HIV type 1 replication

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

A Tat subunit vaccine confers protective immunity against the immune-modulating activity of the human immunodeficiency virus type-1 Tat protein in mice

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Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4⁺T cell hyperactivation and HIV type 1 replication

Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4⁺T cell hyperactivation and HIV type 1 replication