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dc.contributor.author
Silveira, G. F.
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Strottmann, D. M.
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de Borba, Luana
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Mansur, D. S.
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Zanchin, N. I. T.
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Bordignon, J.
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Duarte dos Santos, C.N.
dc.date.available
2017-09-20T18:26:15Z
dc.date.issued
2015-10
dc.identifier.citation
Silveira, G. F.; Strottmann, D. M.; de Borba, Luana; Mansur, D. S.; Zanchin, N. I. T.; et al.; Single point mutations in the helicase domain of the NS3 protein enhance dengue virus replicative capacity in human monocyte-derived dendritic cells and circumvent the type I interferon response; Wiley Blackwell Publishing, Inc; Clinical and Experimental Immunology; 183; 1; 10-2015; 114-128
dc.identifier.issn
0009-9104
dc.identifier.uri
http://hdl.handle.net/11336/24710
dc.description.abstract
Dengue is the most prevalent arboviral disease worldwide. The outcome of the infection is determined by the interplay of viral and host factors. In the present study, we evaluated the cellular response of human monocyte-derived DCs (mdDCs) infected with recombinant dengue virus type 1 (DV1) strains carrying a single point mutation in the NS3hel protein (L435S or L480S). Both mutated viruses infect and replicate more efficiently and produce more viral progeny in infected mdDCs compared with the parental, non-mutated virus (vBACDV1). Additionally, global gene expression analysis using cDNA microarrays revealed that the mutated DVs induce the up-regulation of the interferon (IFN) signalling and pattern recognition receptor (PRR) canonical pathways in mdDCs. Pronounced production of type I IFN were detected specifically in mdDCs infected with DV1-NS3hel-mutated virus compared with mdDCs infected with the parental virus. In addition, we showed that the type I IFN produced by mdDCs is able to reduce DV1 infection rates, suggesting that cytokine function is effective but not sufficient to mediate viral clearance of DV1-NS3hel-mutated strains. Our results demonstrate that single point mutations in subdomain 2 have important implications for adenosine triphosphatase (ATPase) activity of DV1-NS3hel. Although a direct functional connection between the increased ATPase activity and viral replication still requires further studies, these mutations speed up viral RNA replication and are sufficient to enhance viral replicative capacity in human primary cell infection and circumvent type I IFN activity. This information may have particular relevance for attenuated vaccine protocols designed for DV.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley Blackwell Publishing, Inc
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Dendritic Cells
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Dengue Virus
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Ns3 Helicase
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Type I Ifn
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Viral Replicative Capacity
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Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Single point mutations in the helicase domain of the NS3 protein enhance dengue virus replicative capacity in human monocyte-derived dendritic cells and circumvent the type I interferon response
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-09-08T20:08:10Z
dc.identifier.eissn
1365-2249
dc.journal.volume
183
dc.journal.number
1
dc.journal.pagination
114-128
dc.journal.pais
Reino Unido
dc.journal.ciudad
Oxford
dc.description.fil
Fil: Silveira, G. F.. Instituto Carlos Chagas; Brasil
dc.description.fil
Fil: Strottmann, D. M.. Instituto Carlos Chagas; Brasil
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Fil: de Borba, Luana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Instituto Carlos Chagas; Brasil
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Fil: Mansur, D. S.. Universidade Federal Da Santa Catarina; Brasil
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Fil: Zanchin, N. I. T.. Instituto Carlos Chagas; Brasil
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Fil: Bordignon, J.. Instituto Carlos Chagas; Brasil
dc.description.fil
Fil: Duarte dos Santos, C.N.. Instituto Carlos Chagas; Brasil
dc.journal.title
Clinical and Experimental Immunology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/cei.12701
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1111/cei.12701
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