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  • Oral presentation
  • Open Access

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

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Retrovirology20063 (Suppl 1) :S68

  • Published:


  • 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

Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, Maryland
University of Maryland, Baltimore County, USA
Morgan State University, Baltimore, Maryland, USA


© Pati et al; licensee BioMed Central Ltd. 2006

This article is published under license to BioMed Central Ltd.