Rotavirus RNA replication and gene expression.

Abstract

Rotavirus mRNAs are capped but non-polyadenylated and serve as templates for both the synthesis of viral proteins and the segmented dsRNA genome. Viral proteins involved in RNA replication include the RNA polymerase (VP1), the core scaffold protein (VP2) and the non-structural RNA-binding proteins (NSP2 and NSP5). VP2 enhances dsRNA synthesis in vitro, possibly by forming platform structures on which VP1 functions. NSP2 octamers have NTPase and helix-destabilizing activity, and in conjunction with the phosphoprotein NSP5, are proposed to facilitate RNA packaging. The structure of the mRNA template contributes importantly to RNA replication. In particular, base-pairing between the 5' and 3'-ends of viral mRNA generates panhandle structures which promote minus-strand synthesis. For the group A rotaviruses, the 3'-consensus sequence, 5'-UGUGACC-3', which extends as a 3'-tail from the panhandles, also contributes to efficient minus-strand synthesis. Besides containing cis-acting replication signals, the 3'-end of viral mRNAs contains information that stimulates gene expression in infected cells. Specifically, the last four nucleotides of the 3'-consensus sequence, 5'-GACC-3', operate as a virus-specific translation enhancer (3'TE) via a process thought to involve recognition of the element by NSP3. The NSP3-3'TE complex may mimic the function of complexes formed by eukaryotic poly(A)-tails and poly(A)-binding protein, thereby promoting more efficient translation of viral mRNAs.