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      Chlorogenic Acid Inhibits the Replication and Viability of Enterovirus 71 In Vitro

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          Abstract

          Enterovirus 71 (EV71) is an etiology for a number of diseases in humans. Traditional Chinese herbs have been reported to be effective for treating EV71 infection. However, there is no report about the antiviral effects of CHA against EV71. In this study, plaque reduction assay demonstrated that the inhibitory concentration 50% (IC50) of CHA on EV71 replication is 6.3 µg/ml. When both CHA (20 µg/ml) and EV71 were added, or added post-infection at different time points, CHA was able to effectively inhibit EV71 replication between 0 and 10 h. In addition, CHA inhibited EV71 2A transcription and translation in EV71-infected RD cells, but did not affect VP1, 3C, and 3D expression. Furthermore, CHA inhibited secretions of IL-6, TNF-α, IFN-γ and MCP-1 in EV71-infected RD cells. Altogether, these results revealed that CHA may have antiviral properties for treating EV71 infection.

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          IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages.

          D V Jovanovic, J Di Battista, J Martel-Pelletier … (1998)
          IL-17 is a newly described, T cell-derived cytokine with ill-defined physiologic properties. As such, we examined the release of proinflammatory mediators by human macrophages in response to recombinant human (rh) IL-17. IL-1beta and TNF-alpha expression and synthesis were up-regulated by rhIL-17 in a dose (ED50 was 50 +/- 9 ng/ml)- and time-dependent fashion, with cytokine accumulation reaching a zenith after 9 h. Release of IL-6, PGE2, IL-10, IL-12, IL-1R antagonist, and stromelysin was also stimulated by rhIL-17. IL-1beta and TNF-alpha mRNA expression levels were controlled by rhIL-17 in a complex manner with an initial 30-min inhibitory phase, and then up-regulation beginning at 1 h and reaching a plateau at about 3 h. The latter expression pattern closely mirrored the nuclear accumulation of the transcription factor nuclear factor-kappaB. cAMP mimetics isobutyl-1-methylxanthine (IBMX), forskolin, PGE2, and cholera toxin reversed rhIL-17-induced release of TNF-alpha, but had no consistent effect on induced IL-1beta synthesis. Induced release of TNF-alpha was also inhibited by serine/threonine protein kinase inhibitors KT-5720 (protein kinase A) and Calphostin C (protein kinase C), mitogen-activated protein kinase kinase inhibitor PD098059, and a nonspecific tyrosine kinase inhibitor, genistein. Calphostin C alone abrogated the rhIL-17-induced release of IL-1beta. The antiinflammatory cytokines IL-4 (p < 0.01) and IL-10 (p < 0.02) completely reversed rhIL-17-stimulated IL-1beta release, while IL-13 and TGF-beta2 were partially effective (59 and 43% diminution, respectively). IL-10 exerted a significant suppressive effect on IL-17-induced TNF-alpha release (99%, p < 0.02), while the inhibitory effects of IL-4, IL-13, and TGF-beta2 on TNF-alpha secretion were partial (48, 10, and 23%, respectively). The data suggest a pivotal role for IL-17 in initiating and/or sustaining an inflammatory response.
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            Molecular epidemiology and evolution of enterovirus 71 strains isolated from 1970 to 1998.

            B. A. Brown, M. Oberste, J. Alexander … (1999)
            Enterovirus 71 (EV71) (genus Enterovirus, family Picornaviridae), a common cause of hand, foot, and mouth disease (HFMD), may also cause severe neurological diseases, such as encephalitis and poliomyelitis-like paralysis. To examine the genetic diversity and rate of evolution of EV71, we have determined and analyzed complete VP1 sequences (891 nucleotides) for 113 EV71 strains isolated in the United States and five other countries from 1970 to 1998. Nucleotide sequence comparisons demonstrated three distinct EV71 genotypes, designated A, B, and C. The genetic variation within genotypes (12% or fewer nucleotide differences) was less than the variation between genotypes (16.5 to 19.7%). Strains of all three genotypes were at least 94% identical to one another in deduced amino acid sequence. The EV71 prototype strain, BrCr-CA-70, isolated in California in 1970, is the sole member of genotype A. Strains isolated in the United States and Australia during the period from 1972 to 1988, a 1994 Colombian isolate, and isolates from a large HFMD outbreak in Malaysia in 1997 are all members of genotype B. Although strains of genotype B continue to circulate in other parts of the world, none have been isolated in the United States since 1988. Genotype C contains strains isolated in 1985 or later in the United States, Canada, Australia, and the Republic of China. The annual rate of evolution within both the B and C genotypes was estimated to be approximately 1.35 x 10(-2) substitutions per nucleotide and is similar to the rate observed for poliovirus. The results indicate that EV71 is a genetically diverse, rapidly evolving virus. Its worldwide circulation and potential to cause severe disease underscore the need for additional surveillance and improved methods to identify EV71 in human disease.
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              Human enterovirus 71 and hand, foot and mouth disease.

              N Yip, Susanna Lau, Edward Wong … (2010)
              Hand, foot and mouth disease (HFMD) is generally a benign febrile exanthematous childhood disease caused by human enteroviruses. The route of transmission is postulated to be faeco-oral in developing areas but attributed more to respiratory droplet in developed areas. Transmission is facilitated by the prolonged environmental survival of these viruses and their greater resistance to biocides. Serious outbreaks with neurological and cardiopulmonary complications caused by human enterovirus 71 (HEV-71) seem to be commoner in the Asian Pacific region than elsewhere in the world. This geographical predilection is unexplained but could be related to the frequency of intra- and inter-typic genetic recombinations of the virus, the host populations' genetic predisposition, environmental hygiene, and standard of healthcare. Vaccine development could be hampered by the general mildness of the illness and rapid genetic evolution of the virus. Antivirals are not readily available; the role of intravenous immunoglobulin in the treatment of serious complications should be investigated. Monitoring of this disease and its epidemiology in the densely populated Asia Pacific epicentre is important for the detection of emerging epidemics due to enteroviruses.
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                Author and article information

                Contributors
                Paul G. Thomas: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2013
                Publication date (Electronic): 30 September 2013
                Volume: 8
                Issue: 9
                Electronic Location Identifier: e76007
                Affiliations
                [1 ]Department of Clinical Laboratory, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
                [2 ]Department of Endocrinology, The the Huai-an First Affliated Hospital of Nanjing Medical University, Huaian, Jiangsu, China
                St. Jude Children's Research Hospital, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: XL WS. Performed the experiments: YL XH HP. Analyzed the data: XL LZ QJ. Contributed reagents/materials/analysis tools: XL MS YJ YW. Wrote the manuscript: XL WS.

                Article
                Publisher ID: PONE-D-13-23744
                DOI: 10.1371/journal.pone.0076007
                PMC ID: 3786884
                PubMed ID: 24098754
                SO-VID: d0e57c2b-7490-479f-8fc5-c168b32976ab
                Copyright statement: Copyright @ 2013
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 7 June 2013
                Date accepted : 16 August 2013
                Funding
                This work was supported by Health Department of Jiangsu province, China(grant ky 0904). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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