{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T10:50:20Z","timestamp":1787223020071,"version":"build-2736575974"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2010,7,1]],"date-time":"2010-07-01T00:00:00Z","timestamp":1277942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Intranasal mouse hepatitis virus-1 (MHV-1) infection of susceptible mouse strains mimics some important pathologic features observed in the lungs of severe acute respiratory syndrome (SARS)-coronavirus\u2013infected humans. The pathogenesis of SARS remains poorly understood, although increasing evidence suggests that immunopathology could play an important role. We previously reported that the adaptive immune response plays an important protective role in MHV-1\u2013infected resistant B6 mice and that both CD4 and CD8 T cells play a significant role in the development of morbidity and lung pathology following intranasal MHV-1 infection of susceptible C3H\/HeJ and A\/J mice. In this study, we have identified novel CD4 and CD8 epitopes in MHV-1\u2013infected susceptible and resistant strains of mice. Susceptible C3H\/HeJ mice mount robust and broad MHV-1\u2013specific CD4 T cell responses, whereas in resistant B6 mice, Ag-specific CD8 T cell responses dominate. We also show that previously immunized susceptible C3H\/HeJ mice do not develop any morbidity and are completely protected following a lethal-dose MHV-1 challenge despite mounting only a modest secondary T cell response. Finally, we demonstrate that the resistance displayed by B6 mice is not solely accounted for by the elaboration of a broad and vigorous MHV-1\u2013specific CD8 T cell response, as MHV-1 infection of C3.SW-H2b\/SnJ mice, which mount an equally robust CD8 T cell response of the same specificity, is still associated with significant morbidity. Thus, identification of novel CD4 and CD8 T cell epitopes for MHV-1 permitted high-resolution analyses of pulmonary T cell responses in a mouse model of SARS.<\/jats:p>","DOI":"10.4049\/jimmunol.0902749","type":"journal-article","created":{"date-parts":[[2010,6,17]],"date-time":"2010-06-17T02:45:06Z","timestamp":1276742706000},"page":"1132-1141","source":"Crossref","is-referenced-by-count":29,"title":["T Cell Epitope Specificity and Pathogenesis of Mouse Hepatitis Virus-1\u2013Induced Disease in Susceptible and Resistant Hosts"],"prefix":"10.1093","volume":"185","author":[{"given":"Aaruni","family":"Khanolkar","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross B","family":"Fulton","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lecia L","family":"Epping","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhat-Long","family":"Pham","sequence":"additional","affiliation":[{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilea","family":"Tifrea","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M","family":"Varga","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Iowa , Iowa City, IA 52242"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T","family":"Harty","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Iowa , Iowa City, IA 52242"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,7,15]]},"reference":[{"issue":"12","key":"2025032411391668500_r1","doi-asserted-by":"crossref","first-page":"S88","DOI":"10.1038\/nm1143","article-title":"Severe acute respiratory syndrome","volume":"10","author":"Peiris","year":"2004","journal-title":"Nat. Med."},{"key":"2025032411391668500_r2","doi-asserted-by":"crossref","first-page":"8692","DOI":"10.1128\/JVI.00527-07","article-title":"Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome","volume":"81","author":"Cameron","year":"2007","journal-title":"J. Virol."},{"key":"2025032411391668500_r3","doi-asserted-by":"crossref","first-page":"5490","DOI":"10.4049\/jimmunol.181.8.5490","article-title":"T cell responses to whole SARS coronavirus in humans","volume":"181","author":"Li","year":"2008","journal-title":"J. Immunol."},{"key":"2025032411391668500_r4","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nri1732","article-title":"Immunopathogenesis of coronavirus infections: implications for SARS","volume":"5","author":"Perlman","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"2025032411391668500_r5","doi-asserted-by":"crossref","first-page":"10382","DOI":"10.1128\/JVI.00747-06","article-title":"Murine hepatitis virus strain 1 produces a clinically relevant model of severe acute respiratory syndrome in A\/J mice","volume":"80","author":"De Albuquerque","year":"2006","journal-title":"J. Virol."},{"key":"2025032411391668500_r6","doi-asserted-by":"crossref","first-page":"9258","DOI":"10.1128\/JVI.00355-09","article-title":"Protective and pathologic roles of the immune response to mouse hepatitis virus type 1: implications for severe acute respiratory syndrome","volume":"83","author":"Khanolkar","year":"2009","journal-title":"J. Virol."},{"key":"2025032411391668500_r7","doi-asserted-by":"crossref","first-page":"8946","DOI":"10.1128\/JVI.01857-08","article-title":"Toll-like receptor 4 deficiency increases disease and mortality after mouse hepatitis virus type 1 infection of susceptible C3H mice","volume":"83","author":"Khanolkar","year":"2009","journal-title":"J. Virol."},{"key":"2025032411391668500_r8","doi-asserted-by":"crossref","first-page":"6641","DOI":"10.1073\/pnas.0401939101","article-title":"Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice","volume":"101","author":"Bisht","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032411391668500_r9","doi-asserted-by":"crossref","first-page":"9804","DOI":"10.1073\/pnas.0403492101","article-title":"Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity","volume":"101","author":"Buchholz","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032411391668500_r10","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1128\/JVI.79.5.2678-2688.2005","article-title":"Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region","volume":"79","author":"Chen","year":"2005","journal-title":"J. Virol."},{"key":"2025032411391668500_r11","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.virol.2006.03.049","article-title":"Recombinant adeno-associated virus expressing the receptor-binding domain of severe acute respiratory syndrome coronavirus S protein elicits neutralizing antibodies: Implication for developing SARS vaccines","volume":"353","author":"Du","year":"2006","journal-title":"Virology"},{"key":"2025032411391668500_r12","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.4049\/jimmunol.172.5.2834","article-title":"CD4 T cell-dependent CD8 T cell maturation","volume":"172","author":"Khanolkar","year":"2004","journal-title":"J. Immunol."},{"key":"2025032411391668500_r13","doi-asserted-by":"crossref","first-page":"7799","DOI":"10.1128\/JVI.00840-08","article-title":"Regulation of cytokine production by virus-specific CD8 T cells in the lungs","volume":"82","author":"Fulton","year":"2008","journal-title":"J. Virol."},{"key":"2025032411391668500_r14","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.virol.2005.01.050","article-title":"Identification of murine CD8 T cell epitopes in codon-optimized SARS-associated coronavirus spike protein","volume":"335","author":"Zhi","year":"2005","journal-title":"Virology"},{"key":"2025032411391668500_r15","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/978-1-4615-1325-4_46","article-title":"CD8 T cell mediated immunity to neurotropic MHV infection","volume":"494","author":"Bergmann","year":"2001","journal-title":"Adv. Exp. Med. Biol."},{"key":"2025032411391668500_r16","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1099\/0022-1317-77-2-315","article-title":"The JHM strain of mouse hepatitis virus induces a spike protein-specific Db-restricted cytotoxic T cell response","volume":"77","author":"Bergmann","year":"1996","journal-title":"J. Gen. Virol."},{"key":"2025032411391668500_r17","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/978-1-4615-2996-5_75","article-title":"Establishment of MHV-A59 S protein specific cytotoxic T lymphocyte clones","volume":"342","author":"Kyuwa","year":"1993","journal-title":"Adv. Exp. Med. Biol."},{"key":"2025032411391668500_r18","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0042-6822(92)90697-N","article-title":"Mouse hepatitis virus nucleocapsid protein-specific cytotoxic T lymphocytes are Ld restricted and specific for the carboxy terminus","volume":"189","author":"Stohlman","year":"1992","journal-title":"Virology"},{"key":"2025032411391668500_r19","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/978-1-4684-5823-7_78","article-title":"Immunopathogenesis of demyelination induced by MHV-4","volume":"276","author":"Fleming","year":"1990","journal-title":"Adv. Exp. Med. Biol."},{"key":"2025032411391668500_r20","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.4049\/jimmunol.133.2.1016","article-title":"Production and characterization of T cell clones specific for mouse hepatitis virus, strain JHM: in vivo and in vitro analysis","volume":"133","author":"Woodward","year":"1984","journal-title":"J. Immunol."},{"key":"2025032411391668500_r21","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s002510050595","article-title":"SYFPEITHI: database for MHC ligands and peptide motifs","volume":"50","author":"Rammensee","year":"1999","journal-title":"Immunogenetics"},{"key":"2025032411391668500_r22","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.4049\/jimmunol.162.7.3933","article-title":"Cross-recognition of two middle T protein epitopes by immunodominant polyoma virus-specific CTL","volume":"162","author":"Wilson","year":"1999","journal-title":"J. Immunol."},{"key":"2025032411391668500_r23","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1126\/science.1155209","article-title":"Coordination of early protective immunity to viral infection by regulatory T cells","volume":"320","author":"Lund","year":"2008","journal-title":"Science"},{"key":"2025032411391668500_r24","first-page":"3266","article-title":"Tregs control the development of symptomatic West Nile virus infection in humans and mice","volume":"119","author":"Lanteri","year":"2009","journal-title":"J. Clin. Invest."},{"key":"2025032411391668500_r25","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s002510050242","article-title":"On naming H2 haplotypes: functional significance of MHC class Ib alleles","volume":"46","author":"Fischer Lindahl","year":"1997","journal-title":"Immunogenetics"},{"key":"2025032411391668500_r26","doi-asserted-by":"crossref","first-page":"948","DOI":"10.4049\/jimmunol.180.2.948","article-title":"Intranasal vaccination of recombinant adeno-associated virus encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces strong mucosal immune responses and provides long-term protection against SARS-CoV infection","volume":"180","author":"Du","year":"2008","journal-title":"J. Immunol."},{"key":"2025032411391668500_r27","doi-asserted-by":"crossref","first-page":"6981","DOI":"10.1016\/j.vaccine.2007.06.047","article-title":"Priming with SARS CoV S DNA and boosting with SARS CoV S epitopes specific for CD4+ and CD8+ T cells promote cellular immune responses","volume":"25","author":"Huang","year":"2007","journal-title":"Vaccine"},{"key":"2025032411391668500_r28","doi-asserted-by":"crossref","first-page":"4905","DOI":"10.1016\/j.vaccine.2006.03.058","article-title":"Immunization with SARS-CoV S DNA vaccine generates memory CD4+ and CD8+ T cell immune responses","volume":"24","author":"Huang","year":"2006","journal-title":"Vaccine"},{"key":"2025032411391668500_r29","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1016\/j.micinf.2006.05.008","article-title":"Human memory T cell responses to SARS-CoV E protein","volume":"8","author":"Peng","year":"2006","journal-title":"Microbes Infect."},{"key":"2025032411391668500_r30","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.virol.2006.03.036","article-title":"Long-lived memory T lymphocyte responses against SARS coronavirus nucleocapsid protein in SARS-recovered patients","volume":"351","author":"Peng","year":"2006","journal-title":"Virology"},{"key":"2025032411391668500_r31","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.clim.2006.05.002","article-title":"Long-lived effector\/central memory T-cell responses to severe acute respiratory syndrome coronavirus (SARS-CoV) S antigen in recovered SARS patients","volume":"120","author":"Yang","year":"2006","journal-title":"Clin. Immunol."},{"key":"2025032411391668500_r32","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.virusres.2007.03.025","article-title":"Animal models and vaccines for SARS-CoV infection","volume":"133","author":"Roberts","year":"2008","journal-title":"Virus Res."},{"key":"2025032411391668500_r33","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1371\/journal.ppat.0030005","article-title":"A mouse-adapted SARS-coronavirus causes disease and mortality in BALB\/c mice","volume":"3","author":"Roberts","year":"2007","journal-title":"PLoS Pathog."},{"key":"2025032411391668500_r34","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.0105-2896.2006.00384.x","article-title":"Programming, demarcating, and manipulating CD8+ T-cell memory","volume":"211","author":"Badovinac","year":"2006","journal-title":"Immunol. Rev."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/185\/2\/1132\/62469508\/0902749.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/185\/2\/1132\/62469508\/0902749.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T21:37:35Z","timestamp":1743197855000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/185\/2\/1132\/7977367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,7]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2010,7,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0902749","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010,7]]},"published":{"date-parts":[[2010,7]]}}}