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 language | English |
|---|---|
| Article number | 49 |
| Journal | Retrovirology |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jun 24 2014 |
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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 journal › Article
}
TY - JOUR
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.
AB - 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.
KW - Antibodies
KW - HIV progression
KW - Tat
KW - Viral load
UR - http://www.scopus.com/inward/record.url?scp=84903945375&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84903945375&partnerID=8YFLogxK
U2 - 10.1186/1742-4690-11-49
DO - 10.1186/1742-4690-11-49
M3 - Article
C2 - 24961156
AN - SCOPUS:84903945375
VL - 11
JO - Retrovirology
JF - Retrovirology
SN - 1742-4690
IS - 1
M1 - 49
ER -