The replication cycle has been studied in most detail with reovirus 3, a member of the genus Orthoreovirus. The intact virion may enter the cell by receptor-mediated endocytosis, or, alternatively, intermediate subviral particles, resulting from digestion with chymotrypsin in the intestine, may pass into the cytoplasm either via the endosomal pathway or directly. Both types of particles are then degraded to become "core particles," within which the virion-associated transcriptase and capping enzymes repetitively transcribe 5' capped (but not 3' polyadenylated) mRNA molecules, which are extruded through the hollow apices of the icosahedral core particles. Only certain genes are transcribed initially; the others are derepressed following the synthesis of an early viral protein. The mechanism of replication of the genome is complex and not yet fully understood. Various nonstructural and structural viral proteins associate with a complete set of mRNA molecules to form a subviral particle within which complementary minus sense RNA strands are synthesized, producing dsRNA molecules. These in turn serve as templates for the transcription of more mRNA which is translated preferentially to yield a large pool of viral structural proteins. New virions self-assemble and accumulate in cytoplasmic inclusions before being released by cell lysis.
Although the replication of rotaviruses has not yet been studied in so much detail, it is apparent that the general principles are similar. However, certain distinctive features mark the early and late stages of the rotavirus replication cycle. Rotaviruses bind to sialic acid on receptors, via a ligand on the outer capsid hemagglutinating protein VP4; cleavage of VP4 by trypsin is required to enable the virion to enter the cytoplasm, which apparently occurs
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