The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses
Open accessAbstract
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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Cites
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Randomised placebo-controlled trial of ritonavir in advanced HIV-1 disease
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Cited by
Strategies for MMP inhibition in cancer: innovations for the post-trial era
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The proteasome: a suitable antineoplastic target
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Proteasome Inhibitors: An Expanding Army Attacking a Unique Target
Kisselev, A. F., van der Linden, W. A., & Overkleeft, H. S. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.01.003 · Cited by 527
Metadata
- Authors
- André, P., Groettrup, M., Klenerman, P., de Giuli, R., Booth, B. L., Cerundolo, V., Bonneville, M., Jotereau, F., Zinkernagel, R. M., & Lotteau, V.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-10-27
- Volume
- 95
- Issue
- 22
- Pages
- 13120-13124
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2024789710
- Cited by
- 279
- References
- 24
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- green
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- André, P., Groettrup, M., Klenerman, P., de Giuli, R., Booth, B. L., Cerundolo, V., Bonneville, M., Jotereau, F., Zinkernagel, R. M., & Lotteau, V. (1998). An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.95.22.13120
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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