Double Stranded RNA Viruses

The only viruses with dsRNA genomes that are known to infect mammals are some members of the Reoviridae including the orthoreoviruses. Orthoreoviruses, commonly called reoviruses as they are the founding members of the family, are naked (non-enveloped) virions that possess a segmented dsRNA genome consisting of ten segments of fully complementary dsRNA that fall into three size classes; the total size of the 3 L, 3 M and 4 S-sized segments is * 23.5 kbp of dsRNA (Gomatos and Tamm 1963; Joklik 1981; Knipe et al. 2007). Replication of reoviruses occurs within the cytoplasm of the infected host. RNA transcription is by a virion core-associated dsRNA-dependent ssRNA polymerase that utilizes the dsRNA segments as templates for production of plus-sense transcripts that then serve as mRNA and also as templates for synthesis of progeny dsRNA during subviral particle morphogenesis. Despite over 20 kbp of naturally occurring dsRNA, relatively little is known regarding the roles, if any, that ADARs may play in reovirus replication and pathogenesis. What is clear is that reovirus multiplication occurs to high yields in many lines of cultured mammalian cells that possess both ADARs and also functional RNA interference machinery, both of which act on dsRNA. These observations suggest that the reovirus dsRNA is shielded from the host cell's defense machinery. Indeed, no free reovirus dsRNA is normally found in infected cells; as far as is known, reovirus dsRNA is present only enclosed in viral particles (Joklik 1981; Knipe et al. 2007). The yield of infectious Dearing strain reovirus in MEF cells genetically deficient for the cytoplasmic deaminase form, ADAR1 p150, is comparable to that seen in wild-type MEFs in the absence of IFN treatment; furthermore, type I IFN treatment reduces the yield of reovirus comparably in the Adar1 p!50+/+ WT and p150-/- mutant cells (Ward et al. 2011).

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