The role of inducible nitric oxide synthase in the host response to Coxsackievirus myocarditis

The role of inducible nitric oxide synthase in the host response to Coxsackievirus myocarditis

^*Division of Cardiology, Department of Medicine, School of Medicine, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205; ^‡The Wolfson Institute for Biomedical Research, University College, London, United Kingdom; and ^†Department of Immunology, University of Glasgow, Glasgow, United Kingdom

Communicated by Victor A. McKusick, The Johns Hopkins University, Baltimore, MD (received for review October 27, 1997)

Abstract

The host response to Coxsackievirus infection is complex, including T lymphocytes, B lymphocytes, natural killer cells, and macrophages. Although Coxsackievirus infection induces expression of inducible nitric oxide synthase (NOS2; EC 1.14.13.39) in macrophages, the precise role of NOS2 in the host response to Coxsackievirus myocarditis has been unclear. We show, by using mice homozygous for a disrupted NOS2 allele, that Coxsackievirus replicates to higher titers in NOS2^−/− mice, that the host lacking NOS2 clears virus more slowly than the wild-type host, and that myocarditis is much more severe in infected NOS2^−/− mice. These data show that NOS2 is crucial for the host response to Coxsackievirus in the mouse.

nitric oxide

Footnotes

↵ § To whom reprint requests should be addressed at: Division of Cardiology, Dept. of Medicine, The Johns Hopkins University School of Medicine, 950 Ross Bldg., 720 Rutland Ave., Baltimore, MD 21205. e-mail: clowenst{at}welchlink.welch.jhu.edu.
ABBREVIATIONS:

CVB3,

Coxsackievirus strain B type 3;

NK,

natural killer;

NOS2,

inducible nitric oxide synthase;

NOS,

nitric-oxide synthase;

pfu,

plaque-forming units;

RT,

reverse transcription;

IRF-1,

interferon regulatory factor 1