Abstract
The rotavirus (RV) genome consists of 11 double-stranded RNA segments. Sometimes, partial sequence duplication of an RNA segment leads to a rearranged RNA segment. To specify the impact of rearrangement, the replication efficiencies of human RV with rearranged segments 7, 11 or both were compared to these of the homologous human wild-type RV (wt-RV) and of the bovine wt-RV strain RF. As judged by viral growth curves, rotaviruses with a rearranged genome (r-RV) had no selective growth advantage over the homologous wt-RV. In contrast, r-RV were selected over wt-RV during competitive experiments (i.e mixed infections between r-RV and wt-RV followed by serial passages in cell culture). Moreover, when competitive experiments were performed between a human r-RV and the bovine wt-RV strain RF, which had a clear growth advantage, rearranged segments 7, 11 or both always segregated in viral progenies even when performing mixed infections at an MOI ratio of 1 r-RV to 100 wt-RV. Lastly, bovine reassortant viruses that had inherited a rearranged segment 7 from human r-RV were generated. Although substitution of wt by rearranged segment 7 did not result in any growth advantage, the rearranged segment was selected in the viral progenies resulting from mixed infections by bovine reassortant r-RV and wt-RV, even for an MOI ratio of 1 r-RV to 107 wt-RV. Lack of selective growth advantage of r-RV over wt-RV in cell culture suggests a mechanism of preferential packaging of the rearranged segments over their standard counterparts in the viral progeny.
Highlights
Group A rotaviruses (RV), members of the Reoviridae family, are a major cause of infantile viral gastroenteritis and are responsible for approximately 600 000 deaths each year [1,2]
The RV genome consists of 11 segments of double-stranded RNA, which can be separated by polyacrylamide gel electrophoresis (PAGE). dsRNA profiles of wild-type RV typically show four size classes of segments according to their molecular weight
Taken together these results indicated that rearranged segments do not confer any selective growth advantage to viruses sharing the same genetic background
Summary
Group A rotaviruses (RV), members of the Reoviridae family, are a major cause of infantile viral gastroenteritis and are responsible for approximately 600 000 deaths each year [1,2]. The RV genome consists of 11 segments of double-stranded RNA (dsRNA), which can be separated by polyacrylamide gel electrophoresis (PAGE). Variations in the mobility of individual RNA segments allow a genetic characterization of RV strains. Some RV strains show unusual dsRNA profiles, in which standard size segments are replaced by rearranged forms of larger size (for a review see [3,4]). Such rotaviruses with a rearranged genome (rRV) were first isolated from chronically infected immunodeficient children [5,6] and animals [7,8,9]. Gene rearrangements can be generated in cell culture by serial passages of RV at high multiplicity of infection (MOI) [10,11,12,13,14]
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