{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:35:39Z","timestamp":1790634939093,"version":"4.1.0"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"17","license":[{"start":{"date-parts":[[2009,9,1]],"date-time":"2009-09-01T00:00:00Z","timestamp":1251763200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Severe acute respiratory syndrome (SARS) is characterized by substantial acute pulmonary inflammation with a high mortality rate. Despite the identification of SARS coronavirus (SARS-CoV) as the etiologic agent of SARS, a thorough understanding of the underlying disease pathogenesis has been hampered by the lack of a suitable animal model that recapitulates the human disease. Intranasal (i.n.) infection of A\/J mice with the CoV mouse hepatitis virus strain 1 (MHV-1) induces an acute respiratory disease with a high lethality rate that shares several pathological similarities with SARS-CoV infection in humans. In this study, we examined virus replication and the character of pulmonary inflammation induced by MHV-1 infection in susceptible (A\/J, C3H\/HeJ, and BALB\/c) and resistant (C57BL\/6) strains of mice. Virus replication and distribution did not correlate with the relative susceptibilities of A\/J, BALB\/c, C3H\/HeJ, and C57BL\/6 mice. In order to further define the role of the host genetic background in influencing susceptibility to MHV-1-induced disease, we examined 14 different inbred mouse strains. BALB.B and BALB\/c mice exhibited MHV-1-induced weight loss, whereas all other strains of<jats:italic>H-2<jats:sup>b<\/jats:sup><\/jats:italic>and<jats:italic>H-2<jats:sup>d<\/jats:sup><\/jats:italic>mice did not show any signs of disease following MHV-1 infection.<jats:italic>H-2<jats:sup>k<\/jats:sup><\/jats:italic>mice demonstrated moderate susceptibility, with C3H\/HeJ mice exhibiting the most severe disease. C3H\/HeJ mice harbor a natural mutation in the gene that encodes Toll-like receptor 4 (TLR4) that disrupts TLR4 signaling. C3H\/HeJ mice exhibit enhanced morbidity and mortality following i.n. MHV-1 infection compared to wild-type C3H\/HeN mice. Our results indicate that TLR4 plays an important role in respiratory CoV pathogenesis.<\/jats:p>","DOI":"10.1128\/jvi.01857-08","type":"journal-article","created":{"date-parts":[[2009,6,25]],"date-time":"2009-06-25T01:09:20Z","timestamp":1245892160000},"page":"8946-8956","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":63,"title":["Toll-Like Receptor 4 Deficiency Increases Disease and Mortality after Mouse Hepatitis Virus Type 1 Infection of Susceptible C3H Mice"],"prefix":"10.1128","volume":"83","author":[{"given":"Aaruni","family":"Khanolkar","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Iowa, Iowa City, Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey M.","family":"Hartwig","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Iowa, Iowa City, Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brayton A.","family":"Haag","sequence":"additional","affiliation":[{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K.","family":"Meyerholz","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa, Iowa City, Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Harty","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Iowa, Iowa City, Iowa 52242"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Varga","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Iowa, Iowa City, Iowa 52242"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13376-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00747-06"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1440"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/01926230252929918"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2006.11.017"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0882-4010(87)90033-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.58.3.869-875.1986"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/423240a"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(03)00367-8"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.7.4683-4690.1996"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.6.4030"},{"key":"e_1_3_2_13_2","first-page":"509","year":"1952","unstructured":"Gledhill, A. 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