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PMID: 4317283 Published · ppublish English Journal Article

The role of interferon in the protective effect of a synthetic double-stranded polyribonucleotide against intranasal vesicular stomatitis virus challenge in mice.

The Journal of clinical investigation ·Vol. 49 ·No. 8 ·1970-08-00 ·Pages 1565-77

De Clercq E, Nuwer MR, Merigan TC

Abstract

Intravenous injection of polyinosinic acid/polycytidylic acid [(poly rI).(poly rC)] offered significant protection against intranasal challenge of young mice with vesicular stomatitis virus (VSV). Optimal protection was obtained when a single dose was administered 2 hr before virus challenge, but repeated doses were effective when started as late as 3 days after virus challenge. The therapeutic ratio or ratio of maximum tolerated dose to minimum effective dose for a single intravenous injection of (poly rI).(poly rC) 2 hr before virus inoculation was >/=8 mg/kg:0.004 mg/kg or >/=200.Dose-response curves for interferon production and antiviral protection by (poly rI).(poly rC) were closely parallel. Equivalent doses of poly rI or poly rC alone did not exert any interferon-inducing capacity or protective effect on intranasal VSV challenge. Several factors, which are known to potentiate or antagonize interferon production, increased or decreased the interferon-inducing capacity and antiviral protection of either (poly rI).(poly rC) or maleic acid/divinyl ether copolymer (MA/DVE) in parallel. Interferon production and antiviral protection by MA/DVE were enhanced by arginine but abolished by prior treatment with MA/DVE; DEAE-dextran (intraperitoneally), kinetin riboside and isopentenyladenosine, and prior injection of endotoxin reduced both interferon production and antiviral protection by (poly rI).(poly rC). Treatment with exogenous interferon in amounts which closely mimicked the levels of circulating interferon produced endogenously by an effective dose of (poly rI).(poly rC) gave protection against intranasal VSV which was identical with that dose of (poly rI).(poly rC). This strongly suggests that interferon production accounts for the whole protective effect of (poly rI).(poly rC) in the intranasal VSV assay.

MeSH Terms
Animals Arginine/pharmacology Cattle Dextrans/pharmacology Drug Antagonism Endotoxins/pharmacology Interferons/administration & dosage,biosynthesis Maleates/pharmacology Nucleosides Nucleotides/administration & dosage Rats Vesicular stomatitis Indiana virus Virus Diseases/prevention & control
Chemicals
Dextrans Endotoxins Maleates Nucleosides Nucleotides Interferons Arginine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
De Clercq E
Nuwer M R
Merigan T C
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54 references, click to expand
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI106374
Published
1970-08-00
Pages
1565-77
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC322636
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI106374 PMC Full Text View journal details
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