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  • Oral presentation
  • Open Access

Ritonavir inhibits NF-AT activation through modulation of the PI-3 kinase/Akt Ppathway

  • 1,
  • 2,
  • 1,
  • 1,
  • 1,
  • 1,
  • 3 and
  • 3
Retrovirology20063 (Suppl 1) :S68

https://doi.org/10.1186/1742-4690-3-S1-S68

  • Published:

Keywords

  • Ritonavir
  • Lipodystrophy
  • Human Herpes
  • Inhibitor Ritonavir
  • Protease Inhibitor Ritonavir

The HIV protease inhibitor ritonavir has activities apparently unrelated to its inhibition of the HIV protease, including anti-tumor activity in vivo and in vitro, induction of lipodystrophy in vivo, proteasome inhibition, and inhibition of NFκ. Here we show that ritonavir inhibits activation of NF-AT induced by PMA plus ionomycin and by the human herpes virus-8 chemokine receptor homologue, vGPCR. Inhibition occurred by modulation of the PI-3 kinase/Akt/GSK-3 pathway. Ritonavir treatment led to decreased Akt phosphorylation and a resultant decrease in GSK-3 phosphorylation and failed to inhibit NF-AT in GSK-3β -/- knockout cells. Inhibition of multiple signaling pathways by ritonavir may partly explain its anti-tumor activities as well as other effects of ritonavir that are unrelated to its anti-retroviral activity. Taken together, the data suggest that ritonavir may have intrinsic immunomodulatory activities. This work was supported in part by grant RO1 CA099905-01 from NCI.

Authors’ Affiliations

(1)
Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, Maryland
(2)
University of Maryland, Baltimore County, USA
(3)
Morgan State University, Baltimore, Maryland, USA

Copyright

© Pati et al; licensee BioMed Central Ltd. 2006

This article is published under license to BioMed Central Ltd.

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