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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

Copyright

© Le Buanec et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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