Mostrar el registro sencillo del ítem
dc.contributor.author
Filomatori, Claudia Veronica
dc.contributor.author
Carballeda, Juan Manuel
dc.contributor.author
Villordo, Sergio
dc.contributor.author
Aguirre, Sebastian
dc.contributor.author
Pallarés, Horacio Martín
dc.contributor.author
Maestre, Ana M.
dc.contributor.author
Sánchez Vargas, Irma
dc.contributor.author
Blair, Carol D.
dc.contributor.author
Fabri, Cintia
dc.contributor.author
Morales, Maria A.
dc.contributor.author
Fernandez Sesma, Ana
dc.contributor.author
Gamarnik, Andrea Vanesa
dc.date.available
2017-08-18T19:51:48Z
dc.date.issued
2017-03
dc.identifier.citation
Filomatori, Claudia Veronica; Carballeda, Juan Manuel; Villordo, Sergio; Aguirre, Sebastian; Pallarés, Horacio Martín; et al.; Dengue virus genomic variation associated with mosquito adaptation defines the pattern of viral non-coding RNAs and fitness in human cells; Public Library of Science; Plos Pathogens; 13; 3; 3-2017; 1-23; e1006265
dc.identifier.issn
1553-7366
dc.identifier.uri
http://hdl.handle.net/11336/22702
dc.description.abstract
The Flavivirus genus includes a large number of medically relevant pathogens that cycle between humans and arthropods. This host alternation imposes a selective pressure on the viral population. Here, we found that dengue virus, the most important viral human pathogen transmitted by insects, evolved a mechanism to differentially regulate the production of viral non-coding RNAs in mosquitos and humans, with a significant impact on viral fitness in each host. Flavivirus infections accumulate non-coding RNAs derived from the viral 3'UTRs (known as sfRNAs), relevant in viral pathogenesis and immune evasion. We found that dengue virus host adaptation leads to the accumulation of different species of sfRNAs in vertebrate and invertebrate cells. This process does not depend on differences in the host machinery; but it was found to be dependent on the selection of specific mutations in the viral 3'UTR. Dissecting the viral population and studying phenotypes of cloned variants, the molecular determinants for the switch in the sfRNA pattern during host change were mapped to a single RNA structure. Point mutations selected in mosquito cells were sufficient to change the pattern of sfRNAs, induce higher type I interferon responses and reduce viral fitness in human cells, explaining the rapid clearance of certain viral variants after host change. In addition, using epidemic and pre-epidemic Zika viruses, similar patterns of sfRNAs were observed in mosquito and human infected cells, but they were different from those observed during dengue virus infections, indicating that distinct selective pressures act on the 3'UTR of these closely related viruses. In summary, we present a novel mechanism by which dengue virus evolved an RNA structure that is under strong selective pressure in the two hosts, as regulator of non-coding RNA accumulation and viral fitness. This work provides new ideas about the impact of host adaptation on the variability and evolution of flavivirus 3'UTRs with possible implications in virulence and viral transmission.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
3'Utr
dc.subject
Point Mutations
dc.subject
Flavivirus
dc.subject
Sfrna
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Dengue virus genomic variation associated with mosquito adaptation defines the pattern of viral non-coding RNAs and fitness in human cells
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-07-18T14:51:10Z
dc.identifier.eissn
1553-7374
dc.journal.volume
13
dc.journal.number
3
dc.journal.pagination
1-23; e1006265
dc.journal.pais
Estados Unidos
dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Filomatori, Claudia Veronica. 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
dc.description.fil
Fil: Carballeda, Juan Manuel. 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
dc.description.fil
Fil: Villordo, Sergio. 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
dc.description.fil
Fil: Aguirre, Sebastian. Cedars Sinai Medical Center; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Pallarés, Horacio Martín. 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
dc.description.fil
Fil: Maestre, Ana M.. Cedars Sinai Medical Center; Estados Unidos
dc.description.fil
Fil: Sánchez Vargas, Irma. State University of Colorado - Fort Collins; Estados Unidos
dc.description.fil
Fil: Blair, Carol D.. State University of Colorado - Fort Collins; Estados Unidos
dc.description.fil
Fil: Fabri, Cintia. Instituto Nacional de Enfermedades Virales Humanas "Dr. Julio I. Maiztegui"; Argentina
dc.description.fil
Fil: Morales, Maria A.. Instituto Nacional de Enfermedades Virales Humanas "Dr. Julio I. Maiztegui"; Argentina
dc.description.fil
Fil: Fernandez Sesma, Ana. Cedars Sinai Medical Center; Estados Unidos
dc.description.fil
Fil: Gamarnik, Andrea Vanesa. 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
dc.journal.title
Plos Pathogens
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/28264033
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1371/journal.ppat.1006265
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006265
Archivos asociados