{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:42:22Z","timestamp":1781106142425,"version":"3.54.1"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"46","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,11,17]]},"abstract":"<jats:p>To mimic events and molecules involved in type 1 insulin-dependent diabetes mellitus (T1D), we previously designed a transgenic (tg) mouse model where the viral nucleoprotein (NP) gene of lymphocytic choriomeningitis virus (LCMV) was expressed in the thymus to delete high affinity antiself (virus) T cells and in insulin-producing \u03b2 cells of the islets of Langerhans. Such tg mice, termed RIP-LCMV, fail to spontaneously develop diabetes. In contrast, when these mice are challenged with LCMV, they develop diabetes as they display hyperglycemia, low to absent levels of pancreatic insulin, and abundant mononuclear cell infiltrates in the islets. However, expressing the adenovirus early region (E3) gene in \u03b2 cells along with the LCMV transgene aborted the T1D. The present study utilizes this combined tg model (RIP LCMV \u00d7 RIP E3) to define the requirement(s) of either pro-apoptotic TNF and Fas pathways or MHC class I up-regulation on \u03b2 cells for virus-induced T1D. Inhibitors to either pathway (TNF\/Fas or MHC class I) are encoded in the E3 gene complex. To accomplish this task either the E3 region encoding the inhibitors of TNF and Fas pathways or the region encoding gp-19, a protein that inhibits transport of MHC class I molecules out of the endoplasmic reticulum were deleted in the RIP LCMV \u00d7 RIP E3 model. Thus only the gp-19 is required to abort the virus-induced T1D. In contrast, removal of TNF- and Fas-pathway inhibitory genes had no effect on E3-mediated prevention of T1D.<\/jats:p>","DOI":"10.1073\/pnas.0910648106","type":"journal-article","created":{"date-parts":[[2009,11,4]],"date-time":"2009-11-04T00:29:58Z","timestamp":1257294598000},"page":"19450-19454","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":7,"title":["Adenovirus E3 MHC inhibitory genes but not TNF\/Fas apoptotic inhibitory genes expressed in \u03b2 cells prevent autoimmune diabetes"],"prefix":"10.1073","volume":"106","author":[{"given":"Marshall S.","family":"Horwitz","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimon","family":"Efrat","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs","family":"Christen","sequence":"additional","affiliation":[{"name":"Pharmazentrum\/ZAFES, Clinic of the Goethe University Frankfurt, 3.222 Theodor-Stern Kai 7, 60590 Frankfurt am Main, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias G.","family":"von Herrath","sequence":"additional","affiliation":[{"name":"Center for Type 1 Diabetes Research, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B. A.","family":"Oldstone","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,11,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90165-U"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(94)90101-5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200422557"},{"key":"e_1_3_3_4_2","first-page":"65","article-title":"Molecular and cellular mechanisms, pathogenesis, and treatment of insulin-dependent diabetes obtained through study of a transgenic model of molecular mimicry","volume":"296","author":"Oldstone MB","year":"2005","unstructured":"MB Oldstone, Molecular and cellular mechanisms, pathogenesis, and treatment of insulin-dependent diabetes obtained through study of a transgenic model of molecular mimicry. Curr Topics Microbiol Immunol 296, 65\u201387 (2005).","journal-title":"Curr Topics Microbiol Immunol"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.7.3284-3292.2000"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.5.1901"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90164-T"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17005"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.12.6838"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.6.3516"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.1997.0131"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.3.531"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.18.9808"},{"key":"e_1_3_3_14_2","first-page":"2355","volume-title":"Fields Virology","author":"Berk A","year":"2007","unstructured":"A Berk, Adenoviridae: The viruses and their replication. Fields Virology, eds DM Knipe, PM Howley (Lippincott, 5th Ed, Philadelphia, PA), pp. 2355\u20132394 (2007).","edition":"5"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.11.1801"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-0895(199806)14:2<129::AID-DMR208>3.0.CO;2-V"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/smim.1997.0108"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117188"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.37.7.916"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.12.6292"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0109"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.5.2143"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.7.989"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198508083130604"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03860.x"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700442104"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1276-0"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008864200"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1998.9593"},{"key":"e_1_3_3_30_2","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.4049\/jimmunol.161.9.5087","article-title":"In vivo treatment with a MHC class I restricted blocking peptide can prevent virus-induced autoimmune diabetes","volume":"161","author":"von Herrath MG","year":"1998","unstructured":"MG von Herrath, et al., In vivo treatment with a MHC class I restricted blocking peptide can prevent virus-induced autoimmune diabetes. J Immunol 161, 5087\u20135096 (1998).","journal-title":"J Immunol"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00299027"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)91128-7"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1167728"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/459518a"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.5.1119"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(72)92720-1"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197905243002102"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.35.6.712"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0910648106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T07:30:58Z","timestamp":1685172658000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0910648106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,11,17]]},"references-count":38,"journal-issue":{"issue":"46","published-print":{"date-parts":[[2009,11,17]]}},"alternative-id":["10.1073\/pnas.0910648106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0910648106","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,11,17]]},"assertion":[{"value":"2009-09-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-11-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}