Genetic determinants restricting the reassortment of heterologous NSP2 genes into the simian rotavirus SA11 genome

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dc.contributor.authorMingo, Rebeccaen
dc.contributor.authorZhang, Shuen
dc.contributor.authorLong, Courtney P.en
dc.contributor.authorLaConte, Leslie E. W.en
dc.contributor.authorMcDonald, Sarah M.en
dc.date.accessioned2019-01-04T15:46:39Zen
dc.date.available2019-01-04T15:46:39Zen
dc.date.issued2017-08-24en
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
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.en
dc.description.sponsorshipVirginia Tech Carilion Research Institute; National Institutes of Health [R01-AI116815, R21-AI119588]; Translational Biology, Medicine, and Health Graduate Program at Virginia Techen
dc.format.extent12en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41598-017-08068-wen
dc.identifier.issn2045-2322en
dc.identifier.other9301en
dc.identifier.pmid28839154en
dc.identifier.urihttp://hdl.handle.net/10919/86604en
dc.identifier.volume7en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectreverse geneticsen
dc.subjectwa-likeen
dc.subjectproteinen
dc.subjectconstellationsen
dc.subjectreplicationen
dc.subjectcandidateen
dc.subjectgenotypeen
dc.subjectsystemen
dc.subjectrearrangementsen
dc.subjectmechanismsen
dc.titleGenetic determinants restricting the reassortment of heterologous NSP2 genes into the simian rotavirus SA11 genomeen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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