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PMID: 8390481 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Evidence for antiviral effect of nitric oxide. Inhibition of herpes simplex virus type 1 replication.

The Journal of clinical investigation ·Vol. 91 ·No. 6 ·1993-06-00 ·Pages 2446-52

Croen KD

Abstract

Nitric oxide (NO) has antimicrobial activity against a wide spectrum of infectious pathogens, but an antiviral effect has not been reported. The impact of NO, from endogenous and exogenous sources, on herpes simplex virus type 1 (HSV 1) replication was studied in vitro. HSV 1 replication in RAW 264.7 macrophages was reduced 1,806-fold in monolayers induced to make NO by activation with gamma IFN and LPS. A competitive and a noncompetitive inhibitor of nitric oxide synthetase substantially reduced the antiviral effect of activated RAW macrophages. S-nitroso-L-acetyl penicillamine (SNAP) is a donor of NO and was added to the media of infected monolayers to assess the antiviral properties of NO in the absence of gamma IFN and LPS. A single dose of S-nitroso-L-acetyl penicillamine 3 h after infection inhibited HSV 1 replication in Vero, HEp2, and RAW 264.7 cells in a dose-dependent manner. Neither virucidal nor cytocidal effects of NO were observed under conditions that inhibited HSV 1 replication. Nitric oxide had inhibitory effects, comparable to that of gamma IFN/LPS, on protein and DNA synthesis as well as on cell replication. This report demonstrates that, among its diverse properties, NO has an antiviral effect.

MeSH Terms
Animals Antiviral Agents/pharmacology Cells, Cultured Humans Interferon-gamma/pharmacology Lipopolysaccharides/pharmacology Nitric Oxide/pharmacology,toxicity Penicillamine/analogs & derivatives,pharmacology S-Nitroso-N-Acetylpenicillamine Simplexvirus/drug effects,growth & development Virus Replication/drug effects
Chemicals
Antiviral Agents Lipopolysaccharides Nitric Oxide S-Nitroso-N-Acetylpenicillamine Interferon-gamma Penicillamine
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Croen K D
Department of Internal Medicine, University of Cincinnati College of Medicine, OH 45267-0560.
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI116479
Published
1993-06-00
Pages
2446-52
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC443304
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI116479 PMC Full Text View journal details
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