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Nitric oxide inhibition of coxsackievirus replication in vitro

Nitric oxide is a radical molecule with antibacterial, -parasitic, and -viral properties. We investigated the mechanism of NO inhibition of Coxsackievirus B3 (CVB3) replication in vitro by determining the effect of NO upon a single replicative cycle of CVB3 grown in HeLa cells. Transfection of induc...

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Published in:The Journal of clinical investigation 1997-10, Vol.100 (7), p.1760-1767
Main Authors: Zaragoza, C, Ocampo, C J, Saura, M, McMillan, A, Lowenstein, C J
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container_issue 7
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creator Zaragoza, C
Ocampo, C J
Saura, M
McMillan, A
Lowenstein, C J
description Nitric oxide is a radical molecule with antibacterial, -parasitic, and -viral properties. We investigated the mechanism of NO inhibition of Coxsackievirus B3 (CVB3) replication in vitro by determining the effect of NO upon a single replicative cycle of CVB3 grown in HeLa cells. Transfection of inducible NO synthase cDNA into HeLa cells reduces the number of viral particles produced during a single cycle of growth. Similarly, a noncytotoxic concentration of the NO donor S-nitroso-amino-penicillamine reduces the number of viral particles in a dose-dependent manner. To explore the mechanisms by which NO exerts its antiviral effect, we assayed the attachment, replication, and translation steps of the CVB3 life cycle. NO does not affect the attachment of CVB3 to HeLa cells. However, NO inhibits CVB3 RNA synthesis, as shown by a [3H]uridine incorporation assay, reverse transcription-PCR, and Northern analysis. In addition, NO inhibits CVB3 protein synthesis, as shown by [35S]methionine protein labeling and Western blot analysis of infected cells. Thus, NO inhibits CVB3 replication in part by inhibiting viral RNA synthesis by an unknown mechanism.
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subjects Cell Survival - drug effects
Dose-Response Relationship, Drug
Enterovirus - drug effects
Enterovirus - growth & development
HeLa Cells
Humans
Nitric Oxide - pharmacology
Nitric Oxide Synthase - genetics
Nitric Oxide Synthase - metabolism
Penicillanic Acid - analogs & derivatives
Penicillanic Acid - pharmacology
RNA, Viral - biosynthesis
Transfection
Viral Proteins - biosynthesis
Virus Replication - drug effects
title Nitric oxide inhibition of coxsackievirus replication in vitro
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