{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:40:33Z","timestamp":1791297633428,"version":"4.1.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,10,27]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1073\/pnas.95.22.13120","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:42:40Z","timestamp":1027680160000},"page":"13120-13124","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":228,"title":["An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses"],"prefix":"10.1073","volume":"95","author":[{"given":"Patrice","family":"Andr\u00e9","sequence":"first","affiliation":[{"name":"Institut Nationale de la Sant\u00e9 et de la Recherche M\u00e9dicale U98X, Ecole Normale Sup\u00e9rieure, 46 rue d\u2019Italie, 69364 Lyon Cedex 07, France; Research Department, Cantonal Hospital St. Gall, CH-9007 St. Gallen, Switzerland; Institute for Experimental Immunology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Molecular Medicine, John Radcliffe Hospital, Nuffield Department of Medicine, Headington, Oxford, OX3 9DS, United Kingdom; and Institut Nationale de la Sant\u00e9 et..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Groettrup","sequence":"additional","affiliation":[{"name":"Institut Nationale de la Sant\u00e9 et de la Recherche M\u00e9dicale U98X, Ecole Normale Sup\u00e9rieure, 46 rue d\u2019Italie, 69364 Lyon Cedex 07, France; Research Department, Cantonal Hospital St. Gall, CH-9007 St. Gallen, Switzerland; Institute for Experimental Immunology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Molecular Medicine, John Radcliffe Hospital, Nuffield Department of Medicine, Headington, Oxford, OX3 9DS, United Kingdom; and Institut Nationale de la Sant\u00e9 et..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Institut Nationale de la Sant\u00e9 et de la Recherche M\u00e9dicale U98X, Ecole Normale Sup\u00e9rieure, 46 rue d\u2019Italie, 69364 Lyon Cedex 07, France; Research Department, Cantonal Hospital St. Gall, CH-9007 St. Gallen, Switzerland; Institute for Experimental Immunology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Molecular Medicine, John Radcliffe Hospital, Nuffield Department of Medicine, Headington, Oxford, OX3 9DS, United Kingdom; and Institut Nationale de la Sant\u00e9 et..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"de Giuli","sequence":"additional","affiliation":[{"name":"Institut Nationale de la Sant\u00e9 et de la Recherche M\u00e9dicale U98X, Ecole Normale Sup\u00e9rieure, 46 rue d\u2019Italie, 69364 Lyon Cedex 07, France; Research Department, Cantonal Hospital St. Gall, CH-9007 St. Gallen, Switzerland; Institute for Experimental Immunology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Molecular Medicine, John Radcliffe Hospital, Nuffield Department of Medicine, Headington, Oxford, OX3 9DS, United Kingdom; and Institut Nationale de la Sant\u00e9 et..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Bruce L.","family":"Booth","sequence":"additional","affiliation":[{"name":"Institut Nationale de la Sant\u00e9 et de la Recherche M\u00e9dicale U98X, Ecole Normale Sup\u00e9rieure, 46 rue d\u2019Italie, 69364 Lyon Cedex 07, France; Research Department, Cantonal Hospital St. Gall, CH-9007 St. Gallen, Switzerland; Institute for Experimental Immunology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Molecular Medicine, John Radcliffe Hospital, Nuffield Department of Medicine, Headington, Oxford, OX3 9DS, United Kingdom; and Institut Nationale de la Sant\u00e9 et..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Cerundolo","sequence":"additional","affiliation":[{"name":"Institut Nationale de la Sant\u00e9 et de la Recherche M\u00e9dicale U98X, Ecole Normale Sup\u00e9rieure, 46 rue d\u2019Italie, 69364 Lyon Cedex 07, France; Research Department, Cantonal Hospital St. Gall, CH-9007 St. Gallen, Switzerland; Institute for Experimental Immunology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Molecular Medicine, John Radcliffe Hospital, Nuffield Department of Medicine, Headington, Oxford, OX3 9DS, United Kingdom; and Institut Nationale de la Sant\u00e9 et..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Bonneville","sequence":"additional","affiliation":[{"name":"Institut Nationale de la Sant\u00e9 et de la Recherche M\u00e9dicale U98X, Ecole Normale Sup\u00e9rieure, 46 rue d\u2019Italie, 69364 Lyon Cedex 07, France; Research Department, Cantonal Hospital St. Gall, CH-9007 St. Gallen, Switzerland; Institute for Experimental Immunology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Molecular Medicine, John Radcliffe Hospital, Nuffield Department of Medicine, Headington, Oxford, OX3 9DS, United Kingdom; and Institut Nationale de la Sant\u00e9 et..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francine","family":"Jotereau","sequence":"additional","affiliation":[{"name":"Institut Nationale de la Sant\u00e9 et de la Recherche M\u00e9dicale U98X, Ecole Normale Sup\u00e9rieure, 46 rue d\u2019Italie, 69364 Lyon Cedex 07, France; Research Department, Cantonal Hospital St. Gall, CH-9007 St. Gallen, Switzerland; Institute for Experimental Immunology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Molecular Medicine, John Radcliffe Hospital, Nuffield Department of Medicine, Headington, Oxford, OX3 9DS, United Kingdom; and Institut Nationale de la Sant\u00e9 et..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf M.","family":"Zinkernagel","sequence":"additional","affiliation":[{"name":"Institut Nationale de la Sant\u00e9 et de la Recherche M\u00e9dicale U98X, Ecole Normale Sup\u00e9rieure, 46 rue d\u2019Italie, 69364 Lyon Cedex 07, France; Research Department, Cantonal Hospital St. Gall, CH-9007 St. Gallen, Switzerland; Institute for Experimental Immunology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Molecular Medicine, John Radcliffe Hospital, Nuffield Department of Medicine, Headington, Oxford, OX3 9DS, United Kingdom; and Institut Nationale de la Sant\u00e9 et..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Lotteau","sequence":"additional","affiliation":[{"name":"Institut Nationale de la Sant\u00e9 et de la Recherche M\u00e9dicale U98X, Ecole Normale Sup\u00e9rieure, 46 rue d\u2019Italie, 69364 Lyon Cedex 07, France; Research Department, Cantonal Hospital St. Gall, CH-9007 St. Gallen, Switzerland; Institute for Experimental Immunology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland; Institute of Molecular Medicine, John Radcliffe Hospital, Nuffield Department of Medicine, Headington, Oxford, OX3 9DS, United Kingdom; and Institut Nationale de la Sant\u00e9 et..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,10,27]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5270.1886"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199512073332303"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.7.2484"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5371.1871"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)11431-8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)62892-9"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/517808"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60262-X"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60197-2"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.162.6.2125"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-0934(91)90018-U"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830170202"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7761853"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(88)90397-2"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/382726a0"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5321.2024"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.1.347"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.5.2403"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(96)10051-7"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/386463a0"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830270148"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/174.1.209"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1997.tb01003.x"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)04161-5"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119315"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/34193"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5342.1447"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5322.112"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.40.23808"},{"key":"e_1_3_3_30_2","doi-asserted-by":"crossref","first-page":"4859","DOI":"10.4049\/jimmunol.160.10.4859","volume":"160","author":"Anton L C","year":"1998","unstructured":"L C Anton, H L Snyder, J R Bennink, A Vinitsky, M Orlowski, A Porgador, J W Yewdell J Immunol 160, 4859\u20134868 (1998).","journal-title":"J Immunol"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.95.22.13120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T08:30:30Z","timestamp":1682152230000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.95.22.13120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,10,27]]},"references-count":30,"journal-issue":{"issue":"22","published-print":{"date-parts":[[1998,10,27]]}},"alternative-id":["10.1073\/pnas.95.22.13120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.95.22.13120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,10,27]]},"assertion":[{"value":"1998-09-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-10-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}