Nitric oxide inhibition of coxsackievirus replication in vitro

被引:80
作者
Zaragoza, C [1 ]
Ocampo, CJ [1 ]
Saura, M [1 ]
McMillan, A [1 ]
Lowenstein, CJ [1 ]
机构
[1] JOHNS HOPKINS UNIV, SCH MED, DEPT MED, DIV CARDIOL, BALTIMORE, MD 21205 USA
关键词
enterovirus; myocarditis; autoimmune; nitric oxide synthase; nuclear factor kappa B;
D O I
10.1172/JCI119702
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 [H-3]uridine incorporation assay, reverse transcription-PCR, and Northern analysis, In addition, NO inhibits CVB3 protein synthesis, as shown by [S-35]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.
引用
收藏
页码:1760 / 1767
页数:8
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共 80 条
[1]   Pathogenesis of influenza virus-induced pneumonia: Involvement of both nitric oxide and oxygen radicals [J].
Akaike, T ;
Noguchi, Y ;
Ijiri, S ;
Setoguchi, K ;
Suga, M ;
Zheng, YM ;
Dietzschold, B ;
Maeda, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (06) :2448-2453
[2]   INHIBITORY EFFECT OF NITRIC-OXIDE ON THE REPLICATION OF A MURINE RETROVIRUS IN-VITRO AND IN-VIVO [J].
AKARID, K ;
SINET, M ;
DESFORGES, B ;
GOUGEROTPOCIDALO, MA .
JOURNAL OF VIROLOGY, 1995, 69 (11) :7001-7005
[3]   COMPLETE REPLICATION OF POLIOVIRUS IN-VITRO - PREINITIATION RNA REPLICATION COMPLEXES REQUIRE SOLUBLE CELLULAR FACTORS FOR THE SYNTHESIS OF VPG-LINKED RNA [J].
BARTON, DJ ;
BLACK, EP ;
FLANEGAN, JB .
JOURNAL OF VIROLOGY, 1995, 69 (09) :5516-5527
[4]   INHIBITION OF VESICULAR STOMATITIS-VIRUS INFECTION BY NITRIC-OXIDE [J].
BI, ZB ;
REISS, CS .
JOURNAL OF VIROLOGY, 1995, 69 (04) :2208-2213
[5]   NITRIC-OXIDE - NOVEL BIOLOGY WITH CLINICAL RELEVANCE [J].
BILLIAR, TR .
ANNALS OF SURGERY, 1995, 221 (04) :339-349
[6]   PICORNAVIRUS INTERNAL RIBOSOME ENTRY SEGMENTS - COMPARISON OF TRANSLATION EFFICIENCY AND THE REQUIREMENTS FOR OPTIMAL INTERNAL INITIATION OF TRANSLATION IN-VITRO [J].
BORMAN, AM ;
BAILLY, JL ;
GIRARD, M ;
KEAN, KM .
NUCLEIC ACIDS RESEARCH, 1995, 23 (18) :3656-3663
[7]   CLONED AND EXPRESSED NITRIC-OXIDE SYNTHASE STRUCTURALLY RESEMBLES CYTOCHROME-P-450 REDUCTASE [J].
BREDT, DS ;
HWANG, PM ;
GLATT, CE ;
LOWENSTEIN, C ;
REED, RR ;
SNYDER, SH .
NATURE, 1991, 351 (6329) :714-718
[8]   REGULATION OF NITRIC-OXIDE SYNTHASE ACTIVITY IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1)-INFECTED MONOCYTES - IMPLICATIONS FOR HIV-ASSOCIATED NEUROLOGICAL DISEASE [J].
BUKRINSKY, MI ;
NOTTET, HSLM ;
SCHMIDTMAYEROVA, H ;
DUBROVSKY, L ;
FLANAGAN, CR ;
MULLINS, ME ;
LIPTON, SA ;
GENDELMAN, HE .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (02) :735-745
[9]   MACROPHAGES IN MICE ACUTELY INFECTED WITH LYMPHOCYTIC CHORIOMENINGITIS VIRUS ARE PRIMED FOR NITRIC-OXIDE SYNTHESIS [J].
BUTZ, EA ;
HOSTAGER, BS ;
SOUTHERN, PJ .
MICROBIAL PATHOGENESIS, 1994, 16 (04) :283-295
[10]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159