Abstract
Ritonavir is a potent inhibitor of the protease encoded by the human immunodeficiency virus (HIV)-1 and is clinically applied to suppress HIV-1 replication in AIDS patients. When following up clinical hints pointing at a virus-independent effect of ritonavir on the cytotoxic immune response, we found that ritonavir is a modulator of proteasome activity. It competitively inhibits the chymotrypsin-like activity of the proteasome while the trypsin-like activity is markedly enhanced. Kinetic inhibitor studies revealed that the latter effect is due to binding of ritonavir to a non-catalytic modifier site. In this review we summarize the effects of ritonavir and other proteasome inhibitors on antigen presentation and the antiviral immune response. Moreover, we review experiments which show that selective proteasome inhibitors can serve as immune modulators, a function that could be exploited for the treatment of autoimmune diseases.
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Groettrup, M., de Giuli, R., Schmidtke, G. (2004). Effects of the HIV-1 Protease Inhibitor Ritonavir on Proteasome Activity and Antigen Presentation. In: Adams, J. (eds) Proteasome Inhibitors in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-794-9_17
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DOI: https://doi.org/10.1007/978-1-59259-794-9_17
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-452-4
Online ISBN: 978-1-59259-794-9
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