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  • Open Access

The dual (activating/suppressive) effect of extracellular TatHIV-1 is driven by the infalmmatory microenvironment of infected lymphoid foci

  • 1, 2, 3,
  • 1, 2, 3,
  • 1, 2, 3,
  • 4 and
  • 5Email author
Retrovirology20129 (Suppl 1) :P35

https://doi.org/10.1186/1742-4690-9-S1-P35

  • Published:

Keywords

  • Viral Infection
  • Immune Cell
  • Cell Activation
  • Late Stage
  • Viral Replication

It has been shown that HIV-1 infects activated but not resting CD4+ T cells [1] and that CPE induced by viral replication together with the immunosuppressive effect triggered by extracellular Tat protein [2] 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 [3] 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.

Authors’ Affiliations

(1)
INSERM U976, F-75475 Paris, France
(2)
Sorbonne Paris Cité, Laboratory of Immunology, Dermatology & Oncology, UMR-S 976, Université Paris Diderot, F-75475 Paris, France
(3)
Service de dermatologie, Hopital Saint Louis, F-75010 Paris, France
(4)
Institute of Human Virology, University of Maryland Baltimore, Maryland, USA
(5)
Neovacs SA, Paris, France

References

  1. Zagury D, et al: Long-term cultures of HTLV-III--infected T cells: a model of cytopathology of T-cell depletion in AIDS. Science. 1986, 231 (4740): 85View ArticleGoogle Scholar
  2. Viscidi RP, et al: Inhibition of antigen-induced lymphocyte proliferation by Tat protein from HIV- Science. 1989, 246 (4937): 1606Google Scholar
  3. Ensoli B, et al: Release, uptake, and effects of extracellular human immunodeficiency virus type 1 Tat protein on cell growth and viral transactivation. J Virol. 1993, 67 (1): 277PubMed CentralPubMedGoogle Scholar

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