Notably, in natural HIV infection, anti-Tat Abs are produced by only a small fraction of individuals [17,18], while, in contrast, high Ab titers are produced against all other viral products [19]

Notably, in natural HIV infection, anti-Tat Abs are produced by only a small fraction of individuals [17,18], while, in contrast, high Ab titers are produced against all other viral products [19]. presence of anti-Tat Abs in asymptomatic and treatment-na?ve HIV-infected subjects is associated with containment of CD4+ T-cell loss and viral load and with Atagabalin a delay of disease progression. In fact, no subjects with high anti-Tat Ab Mouse monoclonal to CD16.COC16 reacts with human CD16, a 50-65 kDa Fcg receptor IIIa (FcgRIII), expressed on NK cells, monocytes/macrophages and granulocytes. It is a human NK cell associated antigen. CD16 is a low affinity receptor for IgG which functions in phagocytosis and ADCC, as well as in signal transduction and NK cell activation. The CD16 blocks the binding of soluble immune complexes to granulocytes 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. strong class=”kwd-title” Keywords: HIV progression, Tat, Antibodies, CD4+ T cells, Viral load Findings The HIV-1 Tat protein plays essential roles in the virus life cycle and in pathogenesis [1-9], representing a key HIV virulence factor. Tat is produced very early Atagabalin upon infection [1-5] and is released extracellularly [1,4,5]. By binding to heparan sulfate proteoglycans with its basic region, extracellular Tat accumulates in tissues [4] where it exerts effects on both the virus and the immune system [1-11], making it an optimal target for an immune intervention based on antibody (Ab) responses [12-14]. In particular, extracellular Tat activates virus and cellular gene expression and replication, increasing virus transmission to neighbor cells [1,6-9,15,16]. Further, extracellular Tat binds Env spikes forming a virus entry complex that favors infection of dendritic cells (DC) and efficient transmission to T cells, key target cells in primary infection that will later constitute the virus reservoir [16]. This occurs by redirecting virus entry from the canonical receptors to RGD-binding integrins that Tat uses as receptors to enter DC and other cells of the reticular-endothelial cell system [16]. Of note, by binding the Env CCR5 co-receptor binding sites, Tat shields Env from anti-HIV Abs, thus inhibiting virus neutralization by HIV sera, which, however, can be restored and further increased by anti-Tat Abs either present in natural infection or induced by vaccination [16]. Notably, in natural HIV infection, anti-Tat Abs are produced by only a small fraction of individuals [17,18], while, in contrast, high Ab titers are produced against all other viral products [19]. The reason for such a limited anti-Tat Ab response is unclear. However, Tat has potent immunoregulatory functions [10,11] and its capacity to target, enter and induce DC maturation toward a prevalent Th1 response [10,11] may have implications for the setting of the anti-HIV-1 immune response and in AIDS pathogenesis. In fact, when present, anti-Tat Abs correlate with the asymptomatic state and lower disease progression [20-24]. In particular, a higher prevalence of anti-Tat Abs has been shown in asymptomatic and in non-progressors HIV-1-infected individuals as compared to patients in advanced Atagabalin disease or to fast progressors [20-24]. A cross-sectional and longitudinal study, on 252 HIV-1 seroconverters, with a median follow-up time of 7.2?years, indicated that the presence of anti-Tat Abs is predictive of a slower progression to AIDS or immunodeficiency [21]. Progression was faster in persistently anti-Tat Ab-negative than in transiently anti-Tat Ab-positive subjects, whereas no progression was observed in individuals persistently anti-Tat Ab-positive [21]. On the other hand, Tat vaccination in monkeys can prevent or control infection with pathogenic SHIV [25], and this correlates with Tat-specific Abs [12,26]. Thus, anti-Tat Abs may represent a predictive biomarker of a slower progression to AIDS. The effects of anti-Tat Abs on the immunological, virological and clinical outcome of HIV-infected subjects were assessed in a prospective observational study (ISS OBS T-003, ClinicalTrials.gov “type”:”clinical-trial”,”attrs”:”text”:”NCT01029548″,”term_id”:”NCT01029548″NCT01029548) conducted in asymptomatic drug-na?ve HIV-infected adult volunteers enrolled in eight clinical centers in.