The dual (activating/suppressive) effect of extracellular TatHIV-1 is driven by the infalmmatory microenvironment of infected lymphoid foci
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KeywordsViral Infection Immune Cell Cell Activation Late Stage Viral Replication
It has been shown that HIV-1 infects activated but not resting CD4+ T cells  and that CPE induced by viral replication together with the immunosuppressive effect triggered by extracellular Tat protein  account for the decrease of CD4+ T cell count in infected patients. In lymphoid foci, dependent on the level of viral infection, the stromal microenvironment surrounding immune cells could include, together with extracellular Tat  and circulating antiviral IFN-α, inflammatory innate factors such as ATP and derivatives released by CPE-derived dead cells.
We show that, according to its concentration and the presence of inflammatory factors (IFN-α, ATP and ATP-derivatives), Tat protein may exert either an activation with enhanced production of IL2 or an immune suppression of stimulated CD4+ T cells subpopulations.
The double-edged sword of Tat activity on CD4+ T cells could account for its immunopathogenic effects both at the early stage of infection (by allowing CD4+ T cells activation and viral replication) and at late stages (by inducing immuosuppression, source of opportunistic infections). Indications for targeting Tat protein by therapeutic vaccines in subgroups of HIV-1 infected patients will be discussed.
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