Orthoreovirus and Aquareovirus core proteins: conserved enzymatic surfaces, but not protein-protein interfaces

Orthoreoviruses and Aquareoviruses constitute two respective genera in the family Reoviridae of double-stranded RNA viruses. Orthoreoviruses infect mammals, birds, and reptiles and have a genome comprising 10 RNA segments. Aquareoviruses infect fish and have a genome comprising 11 RNA segments. Despite these differences, recent structural and nucleotide sequence evidence indicate that the proteins of Orthoreoviruses and Aquareoviruses share many similarities. The focus of this review is on the structure and function of the Orthoreovirus core proteins lambda1, lambda2, lambda3, and sigma2, for which X-ray crystal structures have been recently reported. The homologous core proteins in Aquareoviruses are VP3, VP1, VP2, and VP6, respectively. By mapping the locations of conserved residues onto the Orthoreovirus crystal structures, we have found that enzymatic surfaces involved in mRNA synthesis are well conserved between these two groups of viruses, whereas several surfaces involved in protein-protein interactions are not well conserved. Other evidence indicates that the Orthoreovirus mu2 and Aquareovirus VP5 proteins are homologous, suggesting that VP5 is a core protein as mu2 is known to be. These findings provide further evidence that Orthoreoviruses and Aquareoviruses have diverged from a common ancestor and contribute to a growing understanding of the functions of the core proteins in viral mRNA synthesis.