Logo image
Back
T cell epitope specificity and pathogenesis of mouse hepatitis virus-1-induced disease in susceptible and resistant hosts
Journal article   Peer reviewed

T cell epitope specificity and pathogenesis of mouse hepatitis virus-1-induced disease in susceptible and resistant hosts

Aaruni Khanolkar, Ross B Fulton, Lecia L Epping, Nhat-Long Pham, Dilea Tifrea, Steven M Varga and John T Harty
The Journal of immunology (1950), Vol.185(2), pp.1132-1141
07/15/2010
DOI: 10.4049/jimmunol.0902749
PMCID: PMC2897948
PMID: 20554960

View Online

Abstract

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-infected 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-infected 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-infected susceptible and resistant strains of mice. Susceptible C3H/HeJ mice mount robust and broad MHV-1-specific 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-specific CD8 T cell response, as MHV-1 infection of C3.SW-H2(b)/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.
 SARS Virus - immunology Species Specificity Humans Severe Acute Respiratory Syndrome - immunology Disease Susceptibility - etiology Interferon-gamma - metabolism CD4-Positive T-Lymphocytes - immunology Murine hepatitis virus - immunology Lung - virology Disease Susceptibility - immunology CD8-Positive T-Lymphocytes - metabolism Female Lung - metabolism Epitopes, T-Lymphocyte - immunology Disease Models, Animal Hepatitis, Viral, Animal - immunology Mice, Inbred C57BL Peptides - immunology CD4-Positive T-Lymphocytes - metabolism Mice, Inbred Strains Coronavirus Infections - immunology Mice, Inbred C3H Immunity, Innate - immunology Animals Mice Mice, Inbred BALB C CD8-Positive T-Lymphocytes - immunology Lung - immunology

Details

Metrics

18 Record Views
20 Times Cited - Web of Science
Logo image