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dc.contributor.authorCong, Y.
dc.contributor.authorHart, B.J.
dc.contributor.authorFrieman, M.
dc.date.accessioned2020-03-27T15:13:13Z
dc.date.available2020-03-27T15:13:13Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85044284357&doi=10.1371%2fjournal.pone.0194868&partnerID=40&md5=8aa23d57dafff212fcf6c78a6d48eeac
dc.identifier.urihttp://hdl.handle.net/10713/12395
dc.description.abstractMiddle East respiratory syndrome coronavirus (MERS-CoV) presents an emerging threat to public health worldwide by causing severe respiratory disease in humans with high virulence and case fatality rate (about 35%) since 2012. Little is known about the pathogenesis and innate antiviral response in primary human monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs) upon MERS-CoV infection. In this study, we assessed MERS-CoV replication as well as induction of inflammatory cytokines and chemokines in MDMs and immature and mature MDDCs. Immature MDDCs and MDMs were permissive for MERS-CoV infection, while mature MDDCs were not, with stimulation of proinflammatory cytokine and chemokine upregulation in MDMs, but not in MDDCs. To further evaluate the antiviral activity of well-defined drugs in primary antigen presenting cells (APCs), three compounds (chloroquine, chlorpromazine and toremifine), each with broad-spectrum antiviral activity in immortalized cell lines, were evaluated in MDMs and MDDCs to determine their antiviral effect on MERS-CoV infection. While chloroquine was not active in these primary cells, chlorpromazine showed strong anti-MERS-CoV activity, but it was associated with high cytotoxicity narrowing the potential window for drug utilization. Unlike in established cells, toremifene had marginal activity when tested in antigen presenting cells, with high apparent cytotoxicity, also limiting its potential as a therapeutic option. These results demonstrate the value of testing drugs in primary cells, in addition to established cell lines, before initiating preclinical or clinical studies for MERS treatment and the importance of carefully assessing cytotoxicity in drug screen assays. Furthermore, these studies also highlight the role of APCs in stimulating a robust protective immune response to MERS-CoV infection.en_US
dc.description.urihttps://doi.org/10.1371/journal.pone.0194868en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.ispartofPLoS ONE
dc.subjectmonocyte-derived dendritic cellsen_US
dc.subject.meshMiddle East Respiratory Syndrome Coronavirusen_US
dc.subject.meshRespiratory Tract Diseasesen_US
dc.subject.meshAntiviral Agentsen_US
dc.subject.meshMacrophagesen_US
dc.titleMERS-CoV pathogenesis and antiviral efficacy of licensed drugs in human monocyte-derived antigen-presenting cellsen_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pone.0194868
dc.identifier.pmid29566060
dc.identifier.ispublishedNo


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