The role of inducible nitric oxide synthase in the host response to Coxsackievirus myocarditis.
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.
Zaragoza
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Division of Cardiology, Department of Medicine, School of Medicine, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
Ocampo
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C
Saura
M
M
Leppo
M
M
Wei
X Q
XQ
Quick
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R
Moncada
S
S
Liew
F Y
FY
Lowenstein
C J
CJ
D000818:Animals; D003384:Coxsackievirus Infections / Q000276:immunology / Q000503:physiopathology*; D029822:Enterovirus B, Human / Q000302:isolation & purification; D004790:Enzyme Induction; D006321:Heart / Q000821:virology*; D051379:Mice; D008815:Mice, Inbred Strains; D009205:Myocarditis / Q000473:pathology / Q000503:physiopathology* / Q000821:virology*; D009206:Myocardium / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000096:biosynthesis
D012367:RNA, Viral; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse