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

Barbara Ensoli¹  Fabrizio Ensoli^1,10  Aurelio Cafaro¹  Paolo Monini¹  Massimo Galli^1,12  Andrea Gori⁴  Cristina Mussini⁵  Vito S Mercurio^1,13  Stefano Bonora²  Giovanni Di Perri²  Massimo Di Pietro⁸  Francesco Mazzotta⁸  Laura Sighinolfi⁶  Alessandra Latini^1,11  Guido Palamara^1,11  Emanuele Focà⁹  Carlo Torti⁹  Silvia Nozza⁷  Giuseppe Tambussi⁷  Adriano Lazzarin⁷  Nicoletta Ladisa³  Gioacchino Angarano³  Angela Arancio^1,10  Giovanni Paniccia^1,10  Cecilia Sgadari¹  Olimpia Longo¹  Vittorio Francavilla^1,10  Orietta Picconi¹  Antonella Tripiciano^1,10  Stefania Bellino¹ 

[1]National AIDS Center, Istituto Superiore di Sanità, Rome, Italy

[2]Amedeo di Savoia Hospital, Turin, Italy

[3]Division of Infectious Diseases, University of Bari, Policlinic Hospital, Bari, Italy

[4]Division of Infectious Diseases, San Gerardo Hospital, University of Milan Bicocca, Monza, Italy

[5]Division of Infectious Diseases, University Policlinic of Modena, Modena, Italy

[6]Unit of Infectious Diseases, University Hospital of Ferrara, Ferrara, Italy

[7]Division of Infectious Diseases, S. Raffaele Hospital, Milan, Italy

[8]Unit of Infectious Diseases, S.M. Annunziata Hospital, Florence, Italy

[9]Division of Tropical and Infectious Diseases, Spedali Civili, Brescia, Italy

[10]Pathology and Microbiology, San Gallicano Institute, Istituti Fisioterapici Ospitalieri, Rome, Italy

[11]Department of Infectious Dermatology, San Gallicano Hospital, Rome, Italy

[12]Institute of Tropical and Infectious Diseases, L. Sacco Hospital, University of Milan, Milan, Italy

[13]Department of Infectious Diseases, S. Maria Goretti Hospital, Latina, Italy

关键词: Viral load;    CD4⁺ T cells;    Antibodies;    Tat;    HIV progression;   

Others  :  824643
DOI  :  10.1186/1742-4690-11-49

 received in 2014-03-28, accepted in 2014-06-12,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Bellino et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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