Double Strand RNA Viruses

1. Double Strand RNA Viruses Reoviruses are the best known and most widely distributed viruses that contain ds RNA. They contain 10-12 genome segments totaling 16-27 kb. Virions are icosahedral. Birnaviruses contain two segments of ds RNA and infect vertebrates and arthropods. Virions are icosahedral. Totiviruses are dsRNA viruses of fungi and protozoa. They have a single genome segment. Partiviruses and hypoviruses infect plants and fungi.

2. Reoviridae Reoviruses: Respiratory Enteric Orphan virus three serotypes that infect man (types 1, 2, 3) usually mild upper respiratory disease found world-wide Rotaviruses: Three serotypes cause widespread illness in man: Groups A, B, C Significant agents for diarrheal illnesses Orbiviruses: Most infect vertebrates other than man but Changuinola virus causes disease in humans Coltiviruses: Colorado tick fever virus causes human disease

6. Reovirus Properties • Genome • Double-stranded RNA • 10 gene segments in three size classes (L, M, S) • Total size 23,500 base pairs • Gene segments encode either one or two proteins each. • Gene segments are transcribed into full-length mRNAs. • Plus strands of gene segments have 5' caps. • Nontranslated regions at segment termini are short. • Gene segments can undergo reassortment between virus strains. • Particles • Spherical, with icosahedral (5:3:2) symmetry • Nonenveloped • Total diameter 85 nm (excluding s1 fibers) • Two concentric protein capsids: outer capsid subunits in T=13 lattice, arrangement of inner capsid subunits unknown • 8 structural proteins: 4 proteins in outer capsid (l2, m1 [mostly as cleavage fragments m1N and m1C], s1, and s3) and 4 proteins in inner capsid (l1, l3, m2, and s2) • Subviral particles (ISVPs and cores) can be generated from fully intact particles (virions) by controlled proteolysis. • Cell-attachment protein s1 can extend from the virion and ISVP surface as a long fiber. • Protein l2 forms pentamers that protrude from the core surface.

7. Reovirus Properties (cont’d) • Replication • Fully cytoplasmic • Sialic acid can serve as cell surface receptor for recognition by cell-attachment protein sl. • Proteolytic processing of outer capsid proteins s3 and m1/mlC is essential to infection and can occur either extracellularly or in endo/lysosomes. • Uncoating of parent particles is incomplete: genomic dsRNA does not exit particles to enter the cytoplasm. • Transcription and capping of viral mRNAs occur within particles and are mediated by particle-associated enzymes. • Segment assortment and packaging involves mRNAs. Minus-strand synthesis occurs within assembling particles. • Mature virions are inefficiently released from infected cells by lysis.

10. Reovirus Structure

13. Rotaviruses Widespread viruses that cause diarrheal disease in humans Cause almost one billion cases of diarrhea/year in humans resulting in almost one million deaths Deaths occur primarily in infants in developing countries where rehydration therapy is not widely available Immunity is incomplete and reinfections occur, but the severity of disease following reinfection is less A live virus quadrivalent vaccine developed by NIH was effective in preventing severe disease but led to an increased incidence of intussecption in vaccinated infants led to withdrawal of the vaccine from the U.S. market

21. Persistence of Orbiviruses and Coltiviruses in RBCs Most arboviruses have developed ways to overwinter in their arthropod host Orbiviruses and coltiviruses, in contrast, have evolved ways to persist in RBCs Bluetongue virus, an orbivirus, binds to glycophorins on the surface of a red blood cell where it persists in a nonreplicating state in which it is hidden from the immune system Colorado tick fever virus infects erythrocyte precursors and remains in the mature RBC in a nonreplicating state In either case the virus can remain dormant but infectious for the life of the RBC, which have a half life of about 120 days

23. Transmission of Colorado Tick Fever