Inhibition of enterovirus 71 replication and the viral 3D polymerase by aurintricarboxylic acid
Identifieur interne : 000895 ( Istex/Checkpoint ); précédent : 000894; suivant : 000896Inhibition of enterovirus 71 replication and the viral 3D polymerase by aurintricarboxylic acid
Auteurs : Hui-Chen Hung [Taïwan] ; Tzu-Chun Chen [Taïwan] ; Ming-Yu Fang [Taïwan] ; Kuei-Jung Yen [Taïwan] ; Shin-Ru Shih [Taïwan] ; John T.-A. Hsu [Taïwan] ; Ching-Ping Tseng [Taïwan]Source :
- Journal of Antimicrobial Chemotherapy [ 0305-7453 ] ; 2010.
Abstract
Objectives Enterovirus 71 (EV71) causes serious diseases in humans. The aim of this study was to examine the effects of aurintricarboxylic acid (ATA) on EV71 replication and to explore the underlying mechanism. Methods To measure the activity of ATA in inhibiting the cytopathic effect (CPE) of EV71, a cell-based neutralization (inhibition of virus-induced CPE) assay was performed. The effect of ATA was further confirmed using plaque reduction and viral yield reduction assays. A time of addition assay was performed to identify the mechanisms of ATA's anti-EV71 activity. We examined the effects of ATA on the following key steps involved in virus replication: (i) translation of the internal ribosomal entry site (IRES)-mediated viral polyprotein; (ii) the proteolytic activity of viral proteases 2A and/or 3C; and (iii) the viral 3D RNA-dependent RNA polymerase (RdRp) activity. Results In this study, ATA was found to be a potent inhibitor of the replication of EV71. In the antiviral neutralization assay, ATA exhibited inhibitory activity against EV71 (TW/4643/98) and EV71 (TW/2231/98). Plaque assay further demonstrated that ATA inhibited EV71 replication with an EC50 (effective concentration at which 50% of plaques were removed) of 2.9 µM. Studies on the mechanism of action revealed that ATA targets the early stage of the viral life cycle after viral entry. ATA was able to inhibit the RdRp activity of EV71, while neither the IRES-mediated translation of viral polyprotein nor the viral 3C protease activity was affected. Conclusions Overall, the findings in this study suggest that ATA is able to effectively inhibit EV71 replication through interfering with the viral 3D polymerase.
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DOI: 10.1093/jac/dkp502
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Hsu</name></author><author><name sortKey="Tseng, Ching Ping" sort="Tseng, Ching Ping" uniqKey="Tseng C" first="Ching-Ping" last="Tseng">Ching-Ping Tseng</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:8FFF823E2AF2FABBC6EB1C5F182A322DD7617FB5</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1093/jac/dkp502</idno><idno type="url">https://api.istex.fr/ark:/67375/HXZ-NW4FL4V4-G/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000746</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000746</idno><idno type="wicri:Area/Istex/Curation">000746</idno><idno type="wicri:Area/Istex/Checkpoint">000895</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000895</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Inhibition of enterovirus 71 replication and the viral 3D polymerase by aurintricarboxylic acid</title><author><name sortKey="Hung, Hui Chen" sort="Hung, Hui Chen" uniqKey="Hung H" first="Hui-Chen" last="Hung">Hui-Chen Hung</name><affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu</wicri:regionArea><wicri:noRegion>Hsin-Chu</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Tzu Chun" sort="Chen, Tzu Chun" uniqKey="Chen T" first="Tzu-Chun" last="Chen">Tzu-Chun Chen</name><affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan</wicri:regionArea><wicri:noRegion>Tao-Yuan</wicri:noRegion></affiliation></author><author><name sortKey="Fang, Ming Yu" sort="Fang, Ming Yu" uniqKey="Fang M" first="Ming-Yu" last="Fang">Ming-Yu Fang</name><affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli</wicri:regionArea><wicri:noRegion>Miaoli</wicri:noRegion></affiliation></author><author><name sortKey="Yen, Kuei Jung" sort="Yen, Kuei Jung" uniqKey="Yen K" first="Kuei-Jung" last="Yen">Kuei-Jung Yen</name><affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli</wicri:regionArea><wicri:noRegion>Miaoli</wicri:noRegion></affiliation></author><author><name sortKey="Shih, Shin Ru" sort="Shih, Shin Ru" uniqKey="Shih S" first="Shin-Ru" last="Shih">Shin-Ru Shih</name><affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan</wicri:regionArea><wicri:noRegion>Tao-Yuan</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli</wicri:regionArea><wicri:noRegion>Miaoli</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Clinical Virology Laboratory, Department of Clinical Pathology, Chang Gung Memorial Hospital, Tao-Yuan</wicri:regionArea><wicri:noRegion>Tao-Yuan</wicri:noRegion></affiliation></author><author><name sortKey="Hsu, John T A" sort="Hsu, John T A" uniqKey="Hsu J" first="John T.-A." last="Hsu">John T.-A. Hsu</name><affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu</wicri:regionArea><wicri:noRegion>Hsin-Chu</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli</wicri:regionArea><wicri:noRegion>Miaoli</wicri:noRegion></affiliation></author><author><name sortKey="Tseng, Ching Ping" sort="Tseng, Ching Ping" uniqKey="Tseng C" first="Ching-Ping" last="Tseng">Ching-Ping Tseng</name><affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu</wicri:regionArea><wicri:noRegion>Hsin-Chu</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Taïwan</country></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Taïwan</country><wicri:regionArea>Corresponding author. Room 112 Zhu-Ming Building, 75 Bo-Ai Street, Hsin-Chu, Taiwan</wicri:regionArea><wicri:noRegion>Taiwan</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Antimicrobial Chemotherapy</title><idno type="ISSN">0305-7453</idno><idno type="eISSN">1460-2091</idno><imprint><publisher>Oxford University Press</publisher><date type="published">2010</date><date type="e-published">2010</date><biblScope unit="vol">65</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="676">676</biblScope><biblScope unit="page" to="683">683</biblScope></imprint><idno type="ISSN">0305-7453</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0305-7453</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Objectives Enterovirus 71 (EV71) causes serious diseases in humans. The aim of this study was to examine the effects of aurintricarboxylic acid (ATA) on EV71 replication and to explore the underlying mechanism. Methods To measure the activity of ATA in inhibiting the cytopathic effect (CPE) of EV71, a cell-based neutralization (inhibition of virus-induced CPE) assay was performed. The effect of ATA was further confirmed using plaque reduction and viral yield reduction assays. A time of addition assay was performed to identify the mechanisms of ATA's anti-EV71 activity. We examined the effects of ATA on the following key steps involved in virus replication: (i) translation of the internal ribosomal entry site (IRES)-mediated viral polyprotein; (ii) the proteolytic activity of viral proteases 2A and/or 3C; and (iii) the viral 3D RNA-dependent RNA polymerase (RdRp) activity. Results In this study, ATA was found to be a potent inhibitor of the replication of EV71. In the antiviral neutralization assay, ATA exhibited inhibitory activity against EV71 (TW/4643/98) and EV71 (TW/2231/98). Plaque assay further demonstrated that ATA inhibited EV71 replication with an EC50 (effective concentration at which 50% of plaques were removed) of 2.9 µM. Studies on the mechanism of action revealed that ATA targets the early stage of the viral life cycle after viral entry. ATA was able to inhibit the RdRp activity of EV71, while neither the IRES-mediated translation of viral polyprotein nor the viral 3C protease activity was affected. Conclusions Overall, the findings in this study suggest that ATA is able to effectively inhibit EV71 replication through interfering with the viral 3D polymerase.</div></front></TEI><affiliations><list><country><li>Taïwan</li></country></list><tree><country name="Taïwan"><noRegion><name sortKey="Hung, Hui Chen" sort="Hung, Hui Chen" uniqKey="Hung H" first="Hui-Chen" last="Hung">Hui-Chen Hung</name></noRegion><name sortKey="Chen, Tzu Chun" sort="Chen, Tzu Chun" uniqKey="Chen T" first="Tzu-Chun" last="Chen">Tzu-Chun Chen</name><name sortKey="Fang, Ming Yu" sort="Fang, Ming Yu" uniqKey="Fang M" first="Ming-Yu" last="Fang">Ming-Yu Fang</name><name sortKey="Hsu, John T A" sort="Hsu, John T A" uniqKey="Hsu J" first="John T.-A." last="Hsu">John T.-A. Hsu</name><name sortKey="Hsu, John T A" sort="Hsu, John T A" uniqKey="Hsu J" first="John T.-A." last="Hsu">John T.-A. Hsu</name><name sortKey="Shih, Shin Ru" sort="Shih, Shin Ru" uniqKey="Shih S" first="Shin-Ru" last="Shih">Shin-Ru Shih</name><name sortKey="Shih, Shin Ru" sort="Shih, Shin Ru" uniqKey="Shih S" first="Shin-Ru" last="Shih">Shin-Ru Shih</name><name sortKey="Shih, Shin Ru" sort="Shih, Shin Ru" uniqKey="Shih S" first="Shin-Ru" last="Shih">Shin-Ru Shih</name><name sortKey="Tseng, Ching Ping" sort="Tseng, Ching Ping" uniqKey="Tseng C" first="Ching-Ping" last="Tseng">Ching-Ping Tseng</name><name sortKey="Tseng, Ching Ping" sort="Tseng, Ching Ping" uniqKey="Tseng C" first="Ching-Ping" last="Tseng">Ching-Ping Tseng</name><name sortKey="Tseng, Ching Ping" sort="Tseng, Ching Ping" uniqKey="Tseng C" first="Ching-Ping" last="Tseng">Ching-Ping Tseng</name><name sortKey="Yen, Kuei Jung" sort="Yen, Kuei Jung" uniqKey="Yen K" first="Kuei-Jung" last="Yen">Kuei-Jung Yen</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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