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Journal of Virology, September 2009, p. 9258-9272, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.00355-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Protective and Pathologic Roles of the Immune Response to Mouse Hepatitis Virus Type 1: Implications for Severe Acute Respiratory Syndrome{triangledown}

Aaruni Khanolkar,1,{dagger} Stacey M. Hartwig,1,{dagger} Brayton A. Haag,2 David K. Meyerholz,3 Lecia L. Epping,1 Jodie S. Haring,1,{ddagger} Steven M. Varga,1,2 and John T. Harty1,2*

Department of Microbiology, University of Iowa, Iowa City, Iowa 52242,1 Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa 52242,2 Department of Pathology, University of Iowa, Iowa City, Iowa 522423

Received 17 February 2009/ Accepted 17 June 2009

Intranasal mouse hepatitis virus type 1 (MHV-1) infection of mice induces lung pathology similar to that observed in severe acute respiratory syndrome (SARS) patients. However, the severity of MHV-1-induced pulmonary disease varies among mouse strains, and it has been suggested that differences in the host immune response might account for this variation. It has also been suggested that immunopathology may represent an important clinical feature of SARS. Little is known about the host immune response to MHV-1 and how it might contribute to some of the pathological changes detected in infected mice. In this study we show that an intact type I interferon system and the adaptive immune responses are required for controlling MHV-1 replication and preventing morbidity and mortality in resistant C57BL/6J mice after infection. The NK cell response also helps minimize the severity of illness following MHV-1 infection of C57BL/6J mice. In A/J and C3H/HeJ mice, which are highly susceptible to MHV-1-induced disease, we demonstrate that both CD4 and CD8 T cells contribute to morbidity during primary infection, and memory responses can enhance morbidity and mortality during subsequent reexposure to MHV-1. However, morbidity in A/J and C3H/HeJ mice can be minimized by treating them with immune serum prior to MHV-1 infection. Overall, our findings highlight the role of the host immune response in contributing to the pathogenesis of coronavirus-induced respiratory disease.

* Corresponding author. Mailing address: Department of Microbiology, University of Iowa, 51 Newton Road, 3-530 Bowen Science Building, Iowa City, IA 52242. Phone: (319) 335-9720. Fax: (319) 335-9006. E-mail: john-harty{at}uiowa.edu

{triangledown} Published ahead of print on 1 July 2009.

{dagger} A.K. and S.M.H. contributed equally to this work.

{ddagger} Present address: 354/308 IACC, Department of Chemistry, Biochemistry and Molecular Biology, North Dakota State University, Fargo, ND 58105.

Journal of Virology, September 2009, p. 9258-9272, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.00355-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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