An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses

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1998
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André, Patrice
Klenerman, Paul
Giuli, Rita de
Booth, Bruce L.
Cerundolo, Vincenzo
Bonneville, Marc
Jotereau, Francine
Zinkernagel, Rolf M.
Lotteau, Vincent
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Inhibitors of the protease of HIV-1 have been used successfully for the treatment of HIV-1-infected patients and AIDS disease. We tested whether these protease inhibitory drugs exerted effects in addition to their antiviral activity. Here, we show in mice infected with lymphocytic choriomeningitis virus and treated with the HIV-1 protease inhibitor ritonavir a marked inhibition of antiviral cytotoxic T lymphocyte (CTL) activity and impaired major histocompatibility complex class I-restricted epitope presentation in the absence of direct effects on lymphocytic choriomeningitis virus replication. A potential molecular target was found: ritonavir selectively inhibited the chymotrypsin-like activity of the 20S proteasome. In view of the possible role of T cell-mediated immunopathology in AIDS pathogenesis, the two mechanisms of action (i.e., reduction of HIV replication and impairment of CTL responses) may complement each other beneficially. Thus, the surprising ability of ritonavir to block the presentation of antigen to CTLs may possibly contribute to therapy of HIV infections but potentially also to the therapy of virally induced immunopathology, autoimmune diseases, and transplantation reactions.

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ISO 690ANDRÉ, Patrice, Marcus GRÖTTRUP, Paul KLENERMAN, Rita de GIULI, Bruce L. BOOTH, Vincenzo CERUNDOLO, Marc BONNEVILLE, Francine JOTEREAU, Rolf M. ZINKERNAGEL, Vincent LOTTEAU, 1998. An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses. In: Proceedings of the National Academy of Sciences. 1998, 95(22), pp. 13120-13124. ISSN 0027-8424. Available under: doi: 10.1073/pnas.95.22.13120
BibTex
@article{Andre1998inhib-22240,
  year={1998},
  doi={10.1073/pnas.95.22.13120},
  title={An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses},
  number={22},
  volume={95},
  issn={0027-8424},
  journal={Proceedings of the National Academy of Sciences},
  pages={13120--13124},
  author={André, Patrice and Gröttrup, Marcus and Klenerman, Paul and Giuli, Rita de and Booth, Bruce L. and Cerundolo, Vincenzo and Bonneville, Marc and Jotereau, Francine and Zinkernagel, Rolf M. and Lotteau, Vincent}
}
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