The presence of anti-Tat antibodies in HIV-infected individuals is associated with containment of CD4+ T-cell decay and viral load, and with delay of disease progression: Results of a 3-year cohort study

Stefania Bellino, Antonella Tripiciano, Orietta Picconi, Vittorio Francavilla, Olimpia Longo, Cecilia Sgadari, Giovanni Paniccia, Angela Arancio, Gioacchino Angarano, Nicoletta Ladisa, Adriano Lazzarin, Giuseppe Tambussi, Silvia Nozza, Carlo Torti, Emanuele Focà, Guido Palamara, Alessandra Latini, Laura Sighinolfi, Francesco Mazzotta, Massimo Di PietroGiovanni Di Perri, Stefano Bonora, Vito S. Mercurio, Cristina Mussini, Andrea Gori, Massimo Galli, Paolo Monini, Aurelio Cafaro, Fabrizio Ensoli, Barbara Ensoli

Research output: Contribution to journalArticle

Abstract

Background: Tat is a key HIV-1 virulence factor, which plays pivotal roles in virus gene expression, replication, transmission and disease progression. After release, extracellular Tat accumulates in tissues and exerts effects on both the virus and the immune system, promoting immune activation and virus spreading while disabling the host immune defense. In particular, Tat binds Env spikes on virus particles forming a virus entry complex, which favors infection of dendritic cells and efficient transmission to T cells via RGD-binding integrins. Tat also shields the CCR5-binding sites of Env rendering ineffective virus neutralization by anti-Env antibodies (Abs). This is reversed by the anti-Tat Abs present in natural infection or induced by vaccination.Findings: Here we present the results of a cohort study, showing that the presence of anti-Tat Abs in asymptomatic and treatment-naïve HIV-infected subjects is associated with containment of CD4+ T-cell loss and viral load and with a delay of disease progression. In fact, no subjects with high anti-Tat Ab titers initiated antiretroviral therapy during the three years of follow-up. In contrast, no significant effects were seen for anti-Env and anti-Gag Abs. The increase of anti-Env Ab titers was associated with a reduced risk of starting therapy only in the presence of anti-Tat Abs, suggesting an effect of combined anti-Tat and anti-Env Abs on the Tat/Env virus entry complex and on virus neutralization.Conclusions: Anti-Tat immunity may help delay HIV disease progression, thus, targeting Tat may offer a novel therapeutic intervention to postpone antiretroviral treatment or to increase its efficacy.

Original languageEnglish
Article number49
JournalRetrovirology
Volume11
Issue number1
DOIs
Publication statusPublished - Jun 24 2014

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Viral Load
Disease Progression
Anti-Idiotypic Antibodies
Cohort Studies
HIV
T-Lymphocytes
Viruses
Virus Internalization
Therapeutics
Virus Activation
Virulence Factors
Infection
Integrins
Virion
Dendritic Cells
HIV-1
Immune System
Immunity
Vaccination
Binding Sites

Keywords

  • Antibodies
  • HIV progression
  • Tat
  • Viral load

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases
  • Medicine(all)

Cite this

The presence of anti-Tat antibodies in HIV-infected individuals is associated with containment of CD4+ T-cell decay and viral load, and with delay of disease progression : Results of a 3-year cohort study. / Bellino, Stefania; Tripiciano, Antonella; Picconi, Orietta; Francavilla, Vittorio; Longo, Olimpia; Sgadari, Cecilia; Paniccia, Giovanni; Arancio, Angela; Angarano, Gioacchino; Ladisa, Nicoletta; Lazzarin, Adriano; Tambussi, Giuseppe; Nozza, Silvia; Torti, Carlo; Focà, Emanuele; Palamara, Guido; Latini, Alessandra; Sighinolfi, Laura; Mazzotta, Francesco; Di Pietro, Massimo; Di Perri, Giovanni; Bonora, Stefano; Mercurio, Vito S.; Mussini, Cristina; Gori, Andrea; Galli, Massimo; Monini, Paolo; Cafaro, Aurelio; Ensoli, Fabrizio; Ensoli, Barbara.

In: Retrovirology, Vol. 11, No. 1, 49, 24.06.2014.

Research output: Contribution to journalArticle

Bellino, S, Tripiciano, A, Picconi, O, Francavilla, V, Longo, O, Sgadari, C, Paniccia, G, Arancio, A, Angarano, G, Ladisa, N, Lazzarin, A, Tambussi, G, Nozza, S, Torti, C, Focà, E, Palamara, G, Latini, A, Sighinolfi, L, Mazzotta, F, Di Pietro, M, Di Perri, G, Bonora, S, Mercurio, VS, Mussini, C, Gori, A, Galli, M, Monini, P, Cafaro, A, Ensoli, F & Ensoli, B 2014, 'The presence of anti-Tat antibodies in HIV-infected individuals is associated with containment of CD4+ T-cell decay and viral load, and with delay of disease progression: Results of a 3-year cohort study', Retrovirology, vol. 11, no. 1, 49. https://doi.org/10.1186/1742-4690-11-49
Bellino, Stefania ; Tripiciano, Antonella ; Picconi, Orietta ; Francavilla, Vittorio ; Longo, Olimpia ; Sgadari, Cecilia ; Paniccia, Giovanni ; Arancio, Angela ; Angarano, Gioacchino ; Ladisa, Nicoletta ; Lazzarin, Adriano ; Tambussi, Giuseppe ; Nozza, Silvia ; Torti, Carlo ; Focà, Emanuele ; Palamara, Guido ; Latini, Alessandra ; Sighinolfi, Laura ; Mazzotta, Francesco ; Di Pietro, Massimo ; Di Perri, Giovanni ; Bonora, Stefano ; Mercurio, Vito S. ; Mussini, Cristina ; Gori, Andrea ; Galli, Massimo ; Monini, Paolo ; Cafaro, Aurelio ; Ensoli, Fabrizio ; Ensoli, Barbara. / The presence of anti-Tat antibodies in HIV-infected individuals is associated with containment of CD4+ T-cell decay and viral load, and with delay of disease progression : Results of a 3-year cohort study. In: Retrovirology. 2014 ; Vol. 11, No. 1.
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T1 - The presence of anti-Tat antibodies in HIV-infected individuals is associated with containment of CD4+ T-cell decay and viral load, and with delay of disease progression

T2 - Results of a 3-year cohort study

AU - Bellino, Stefania

AU - Tripiciano, Antonella

AU - Picconi, Orietta

AU - Francavilla, Vittorio

AU - Longo, Olimpia

AU - Sgadari, Cecilia

AU - Paniccia, Giovanni

AU - Arancio, Angela

AU - Angarano, Gioacchino

AU - Ladisa, Nicoletta

AU - Lazzarin, Adriano

AU - Tambussi, Giuseppe

AU - Nozza, Silvia

AU - Torti, Carlo

AU - Focà, Emanuele

AU - Palamara, Guido

AU - Latini, Alessandra

AU - Sighinolfi, Laura

AU - Mazzotta, Francesco

AU - Di Pietro, Massimo

AU - Di Perri, Giovanni

AU - Bonora, Stefano

AU - Mercurio, Vito S.

AU - Mussini, Cristina

AU - Gori, Andrea

AU - Galli, Massimo

AU - Monini, Paolo

AU - Cafaro, Aurelio

AU - Ensoli, Fabrizio

AU - Ensoli, Barbara

PY - 2014/6/24

Y1 - 2014/6/24

N2 - Background: Tat is a key HIV-1 virulence factor, which plays pivotal roles in virus gene expression, replication, transmission and disease progression. After release, extracellular Tat accumulates in tissues and exerts effects on both the virus and the immune system, promoting immune activation and virus spreading while disabling the host immune defense. In particular, Tat binds Env spikes on virus particles forming a virus entry complex, which favors infection of dendritic cells and efficient transmission to T cells via RGD-binding integrins. Tat also shields the CCR5-binding sites of Env rendering ineffective virus neutralization by anti-Env antibodies (Abs). This is reversed by the anti-Tat Abs present in natural infection or induced by vaccination.Findings: Here we present the results of a cohort study, showing that the presence of anti-Tat Abs in asymptomatic and treatment-naïve HIV-infected subjects is associated with containment of CD4+ T-cell loss and viral load and with a delay of disease progression. In fact, no subjects with high anti-Tat Ab titers initiated antiretroviral therapy during the three years of follow-up. In contrast, no significant effects were seen for anti-Env and anti-Gag Abs. The increase of anti-Env Ab titers was associated with a reduced risk of starting therapy only in the presence of anti-Tat Abs, suggesting an effect of combined anti-Tat and anti-Env Abs on the Tat/Env virus entry complex and on virus neutralization.Conclusions: Anti-Tat immunity may help delay HIV disease progression, thus, targeting Tat may offer a novel therapeutic intervention to postpone antiretroviral treatment or to increase its efficacy.

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KW - Antibodies

KW - HIV progression

KW - Tat

KW - Viral load

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