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Journal of Virology, September 1998, p. 7084-7090, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Resistance to Murine Hepatitis Virus Strain 3 Is Dependent on Production of Nitric Oxide

M. Pope,1 P. A. Marsden,2 E. Cole,2 S. Sloan,2 L. S. Fung,2 Q. Ning,2 J. W. Ding,2 J. L. Leibowitz,3 M. J. Phillips,4 and G. A. Levy2,*

Departments of Surgery,1 Medicine,2 and Pathology,4 The University of Toronto, Toronto, Ontario, Canada, and Department of Pathology, Texas A&M University, College Station, Texas3

Received 12 January 1998/Accepted 3 June 1998

The strain-specific spectrum of liver disease following murine hepatitis virus type 3 (MHV-3) infection is dependent on inflammatory mediators released by macrophages. Production of nitric oxide (NO) by macrophages has been implicated in resistance to a number of viruses, including ectromelia virus, vaccinia virus, and herpes simplex virus type 1. This study was undertaken to define the role of NO in MHV-3 infection. Gamma interferon-induced production of NO inhibited growth of MHV-3 in a murine macrophage cell line (RAW 264.7). Viral inhibitory activity was reproduced by the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP), whereas N-acetyl-DL-pencillamine (NAP), an inactive analog of SNAP, had no effect. Electron microscopy studies confirmed the inhibitory effects of NO on viral replication. Peritoneal macrophages isolated from A/J mice known to be resistant to MHV-3 produced a fivefold-higher level of NO and higher levels of mRNA transcripts of inducible NO synthase in response to gamma interferon than macrophages from susceptible BALB/cJ mice. SNAP inhibited growth of MHV-3 in macrophages from both strains of mice to similar degrees. In vivo inhibition of NO by N-monomethyl-L-arginine resulted in loss of resistance to MHV-3 in A/J mice. These results collectively demonstrate a defect in the production of NO in macrophages from susceptible BALB/cJ mice and define the importance of endogenous NO in resistance to MHV-3 infection in resistant A/J mice.

* Corresponding author. Mailing address: The Toronto Hospital, 621 University Ave., 10th Floor, Rm. 151, Toronto, Ontario, M5G 2C4 Canada. Phone: (416) 340-5166. Fax: (416) 340-3378. E-mail: fgl2{at}msn.com.

Journal of Virology, September 1998, p. 7084-7090, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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