dc.creatorFilomatori, Claudia Veronica
dc.creatorCarballeda, Juan Manuel
dc.creatorVillordo, Sergio
dc.creatorAguirre, Sebastian
dc.creatorPallarés, Horacio Martín
dc.creatorMaestre, Ana M.
dc.creatorSánchez Vargas, Irma
dc.creatorBlair, Carol D.
dc.creatorFabri, Cintia
dc.creatorMorales, Maria A.
dc.creatorFernandez Sesma, Ana
dc.creatorGamarnik, Andrea Vanesa
dc.date.accessioned2017-08-18T19:51:48Z
dc.date.accessioned2018-11-06T13:43:14Z
dc.date.available2017-08-18T19:51:48Z
dc.date.available2018-11-06T13:43:14Z
dc.date.created2017-08-18T19:51:48Z
dc.date.issued2017-03
dc.identifierFilomatori, 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.identifier1553-7366
dc.identifierhttp://hdl.handle.net/11336/22702
dc.identifier1553-7374
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1878556
dc.description.abstractThe 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.languageeng
dc.publisherPublic Library of Science
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/28264033
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1371/journal.ppat.1006265
dc.relationinfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006265
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subject3'UTR
dc.subjectPOINT MUTATIONS
dc.subjectFLAVIVIRUS
dc.subjectSFRNA
dc.titleDengue virus genomic variation associated with mosquito adaptation defines the pattern of viral non-coding RNAs and fitness in human cells
dc.typeArtículos de revistas
dc.typeArtículos de revistas
dc.typeArtículos de revistas


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