Nitric oxide inhibits viral replication in murine myocarditis.
Nitric oxide (NO) is a radical molecule that not only serves as a vasodilator and neurotransmitter but also acts as a cytotoxic effector molecule of the immune system. The inducible enzyme making NO, inducible NO synthase (iNOS), is transcriptionally activated by IFN-gamma and TNF-alpha, cytokines which are produced during viral infection. We show that iNOS is induced in mice infected with the Coxsackie B3 virus. Macrophages expressing iNOS are identified in the hearts and spleens of infected animals with an antibody raised against iNOS. Infected mice have increased titers of virus and a higher mortality when fed NOS inhibitors. Thus, viral infection induces iNOS in vivo, and NO inhibits viral replication. NO is a novel, nonspecific immune defense against viruses in vivo.
Lowenstein
C J
CJ
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Hill
S L
SL
Lafond-Walker
A
A
Wu
J
J
Allen
G
G
Landavere
M
M
Rose
N R
NR
Herskowitz
A
A
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001120:Arginine / Q000031:analogs & derivatives / Q000633:toxicity; D002460:Cell Line; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000276:immunology / Q000503:physiopathology*; D029822:Enterovirus B, Human / Q000187:drug effects / Q000502:physiology*; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000633:toxicity; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis; D008262:Macrophage Activation; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000276:immunology / Q000503:physiopathology* / Q000821:virology*; D009206:Myocardium / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D011817:Rabbits; D013154:Spleen / Q000201:enzymology; D014158:Transcription, Genetic / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D019323:omega-N-Methylarginine
D000906:Antibodies; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010446:Peptide Fragments; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester