Matches in SemOpenAlex for { <https://semopenalex.org/work/W2464761504> ?p ?o ?g. }
Showing items 1 to 71 of
71
with 100 items per page.
- W2464761504 abstract "Arboviruses cycle through both vertebrates and invertebrates, which requires them to adapt to disparate hosts while maintaining genetic integrity during genome replication. To study the genetic mechanisms and determinants of these processes, we use chikungunya virus (CHIKV), a re-emerging human pathogen transmitted by the Aedes mosquito. We isolated novel mutators with decreased replication fidelity and higher mutation frequencies, allowing us to examine the fitness of error-prone arbovirus variants. Although CHIKV mutators displayed no major replication defects in mammalian cell culture, they were attenuated in vivo. Unexpectedly, mutator phenotypes were suppressed in mosquito cells and the variants exhibited significant defects in RNA synthesis. Consequently, these replication defects resulted in strong selection for reversion during inection of mosquitoes. Since residue 483 is conserved among alphaviruses, we examined the analogous mutations in Sindbis virus (SINV), which also reduced polymerase fidelity and generated replication defects in mosquito cells. However, replication defects were mosquito cell-specific and were not observed in Drosophila S2 cells, allowing us to evaluate the potential attenuation of mutators in insect models where pressure for reversion was absent. Indeed, the SINV mutator variant was attenuated in fruit flies. These findings confirm that residue 483 is a determinant regulating alphavirus polymerase fidelity and demonstrate proof of principle that arboviruses can be attenuated in mammalian and insect hosts by reducing fidelity." @default.
- W2464761504 created "2016-07-22" @default.
- W2464761504 creator A5091560724 @default.
- W2464761504 date "2014-01-01" @default.
- W2464761504 modified "2023-09-24" @default.
- W2464761504 title "Chikungunya virus nonstructural proteins regulate replication fidelity and pathogenicity in vivo" @default.
- W2464761504 hasPublicationYear "2014" @default.
- W2464761504 type Work @default.
- W2464761504 sameAs 2464761504 @default.
- W2464761504 citedByCount "0" @default.
- W2464761504 crossrefType "dissertation" @default.
- W2464761504 hasAuthorship W2464761504A5091560724 @default.
- W2464761504 hasConcept C104317684 @default.
- W2464761504 hasConcept C127716648 @default.
- W2464761504 hasConcept C140704245 @default.
- W2464761504 hasConcept C159047783 @default.
- W2464761504 hasConcept C2522874641 @default.
- W2464761504 hasConcept C2777343345 @default.
- W2464761504 hasConcept C2777474056 @default.
- W2464761504 hasConcept C2778116200 @default.
- W2464761504 hasConcept C2779755945 @default.
- W2464761504 hasConcept C2781273456 @default.
- W2464761504 hasConcept C2781313946 @default.
- W2464761504 hasConcept C54355233 @default.
- W2464761504 hasConcept C67705224 @default.
- W2464761504 hasConcept C70883133 @default.
- W2464761504 hasConcept C82381507 @default.
- W2464761504 hasConcept C86803240 @default.
- W2464761504 hasConceptScore W2464761504C104317684 @default.
- W2464761504 hasConceptScore W2464761504C127716648 @default.
- W2464761504 hasConceptScore W2464761504C140704245 @default.
- W2464761504 hasConceptScore W2464761504C159047783 @default.
- W2464761504 hasConceptScore W2464761504C2522874641 @default.
- W2464761504 hasConceptScore W2464761504C2777343345 @default.
- W2464761504 hasConceptScore W2464761504C2777474056 @default.
- W2464761504 hasConceptScore W2464761504C2778116200 @default.
- W2464761504 hasConceptScore W2464761504C2779755945 @default.
- W2464761504 hasConceptScore W2464761504C2781273456 @default.
- W2464761504 hasConceptScore W2464761504C2781313946 @default.
- W2464761504 hasConceptScore W2464761504C54355233 @default.
- W2464761504 hasConceptScore W2464761504C67705224 @default.
- W2464761504 hasConceptScore W2464761504C70883133 @default.
- W2464761504 hasConceptScore W2464761504C82381507 @default.
- W2464761504 hasConceptScore W2464761504C86803240 @default.
- W2464761504 hasLocation W24647615041 @default.
- W2464761504 hasOpenAccess W2464761504 @default.
- W2464761504 hasPrimaryLocation W24647615041 @default.
- W2464761504 hasRelatedWork W1947565261 @default.
- W2464761504 hasRelatedWork W2050559486 @default.
- W2464761504 hasRelatedWork W2063560310 @default.
- W2464761504 hasRelatedWork W2071932815 @default.
- W2464761504 hasRelatedWork W2074776659 @default.
- W2464761504 hasRelatedWork W2087854601 @default.
- W2464761504 hasRelatedWork W2113911672 @default.
- W2464761504 hasRelatedWork W2120284954 @default.
- W2464761504 hasRelatedWork W2159093669 @default.
- W2464761504 hasRelatedWork W2201596974 @default.
- W2464761504 hasRelatedWork W2535127719 @default.
- W2464761504 hasRelatedWork W2791457130 @default.
- W2464761504 hasRelatedWork W2884924160 @default.
- W2464761504 hasRelatedWork W2898509542 @default.
- W2464761504 hasRelatedWork W2929344305 @default.
- W2464761504 hasRelatedWork W3007599245 @default.
- W2464761504 hasRelatedWork W3138346482 @default.
- W2464761504 hasRelatedWork W3153411761 @default.
- W2464761504 hasRelatedWork W3203270284 @default.
- W2464761504 hasRelatedWork W763093762 @default.
- W2464761504 isParatext "false" @default.
- W2464761504 isRetracted "false" @default.
- W2464761504 magId "2464761504" @default.
- W2464761504 workType "dissertation" @default.