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dc.contributor.authorMingo, Rebecca
dc.contributor.authorZhang, Shu
dc.contributor.authorLong, Courtney P.
dc.contributor.authorLaConte, Leslie E. W.
dc.contributor.authorMcDonald, Sarah M.
dc.date.accessioned2019-01-04T15:46:39Z
dc.date.available2019-01-04T15:46:39Z
dc.date.issued2017-08-24
dc.identifier.issn2045-2322
dc.identifier.other9301
dc.identifier.urihttp://hdl.handle.net/10919/86604
dc.description.abstractRotaviruses (RVs) can evolve through the process of reassortment, whereby the 11 double-stranded RNA genome segments are exchanged among strains during co-infection. However, reassortment is limited in cases where the genes or encoded proteins of co-infecting strains are functionally incompatible. In this study, we employed a helper virus-based reverse genetics system to identify NSP2 gene regions that correlate with restricted reassortment into simian RV strain SA11. We show that SA11 reassortants with NSP2 genes from human RV strains Wa or DS-1 were efficiently rescued and exhibit no detectable replication defects. However, we could not rescue an SA11 reassortant with a human RV strain AU-1 NSP2 gene, which differs from that of SA11 by 186 nucleotides ( 36 amino acids). To map restriction determinants, we engineered viruses to contain chimeric NSP2 genes in which specific regions of AU-1 sequence were substituted with SA11 sequence. We show that a region spanning AU-1 NSP2 gene nucleotides 784-820 is critical for the observed restriction; yet additional determinants reside in other gene regions. In silico and in vitro analyses were used to predict how the 784-820 region may impact NSP2 gene/protein function, thereby informing an understanding of the reassortment restriction mechanism.en_US
dc.description.sponsorshipVirginia Tech Carilion Research Institute; National Institutes of Health [R01-AI116815, R21-AI119588]; Translational Biology, Medicine, and Health Graduate Program at Virginia Tech
dc.format.extent12
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherSpringer Nature
dc.rightsCreative Commons Attribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectreverse genetics
dc.subjectwa-like
dc.subjectprotein
dc.subjectconstellations
dc.subjectreplication
dc.subjectcandidate
dc.subjectgenotype
dc.subjectsystem
dc.subjectrearrangements
dc.subjectmechanisms
dc.titleGenetic determinants restricting the reassortment of heterologous NSP2 genes into the simian rotavirus SA11 genomeen_US
dc.typeArticle - Refereed
dc.description.notesThe authors would like to thank members of the McDonald laboratory for intellectual and technical support. We also thank Dr. John Patton (University of Maryland, College Park) for the generous donation of reagents. This work was supported through start-up funding from the Virginia Tech Carilion Research Institute and through grants from the National Institutes of Health (R01-AI116815 and R21-AI119588). C.P.L. was also supported by the Translational Biology, Medicine, and Health Graduate Program at Virginia Tech.
dc.title.serialScientific Reports
dc.identifier.doihttps://doi.org/10.1038/s41598-017-08068-w
dc.identifier.volume7
dc.type.dcmitypeText
dc.identifier.pmid28839154


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Creative Commons Attribution 4.0 International
License: Creative Commons Attribution 4.0 International