Reoviruses, Rotaviruses and Caliciviruses

1. Reoviruses, Rotaviruses and Caliciviruses • Chapter 37

2. Properties of Reoviruses • Structure • Icosahedral, 60-80 nm, double capsid shell • Segmented, double-stranded RNA; 16-27 kb • 9 structural proteins, several enzymes packaged in virus • Nonenveloped • Cytoplasmic replication • Extremely stable • Heat resistant • Remain infectious after treatment of pH 3-9 • Classification • Respiratory, enteric, orphan • Family Reoviridae • Nine genera

3. Reovirus Replication • Receptor-mediated attachment and endocytosis • Vesicle is targeted to lysosome (fusion) • Drop in pH allows virus to shed its outer capsid • This results in inner capsid escape into the cytoplasm • The RNA transcriptase (a polymerase) is activated • Inner capsid uncoats, releasing RNAs into cytoplasm • Viral mRNA synthesis is initiated • Viral polypeptides are synthesized • A viral replicase synthesizes second RNA strand • Assembly occurs in cytoplasm • Mature virus exits when cell dies from lysis

4. Rotaviruses • Major cause of diarrhea • Similar to reoviruses in morphology and replication strategy • Classification • Five serological groups (A-E) • Group A can be distinguished from others by electophoretic mobility of gene segments • Animal susceptibility • Rotaviruses are highly promiscuous • Major cause of disease in livestock industry • Many young animals can become persistent carriers, shedding virus to other animals • Difficult to propagate in cell culture systems • Often requires infection of animals, then harvesting virus from diarrhea

5. Segment Product Location Function 1 VP1 Inner core RNA polymerase 2 VP2 Inner core RNA-binding protein 3 VP3 Inner core Guanyltransferase 4 VP4 Outer capsid HA, neutralizing antigen, protease, cell attachment 5 NSP1 Nonstructural RNA-binding zinc finger protein (transcription factor) 6 VP6 Inner capsid Trimer, hydrophobic 7 NSP3 Nonstructural RNA-binding protein 8 NSP2 Nonstructural RNA-binding protein 9 VP7 Outer capsid RER integral membrane protein 10 NSP4 Nonstructural RER integral membrane protein 11 NSP5 Nonstructural RNA-binding Rotavirus Gene Segments

6. Rotavirus Pathogenesis • Infect villi of small intestine • Multiply in enterocytes • Distrupts cellular transport systems • Endoplasmic reticulum in particular • Damaged cells slough off and shed virus • Enterocytes are replaced by crypt cells • Crypt cells have different sodium and glucose transport features that lead to fluid loss in the small intestine • Diarrhea ensues

7. Rotavirus Pathogenesis • Clinical findings and laboratory diagnosis • Principally a disease of children • Can be fatal if not treated (hydration) • Diagnostic by ELISA or PCR • Epidemiology and Immunity • 3 to 5 billion cases per year • As many as 5 million deaths • 50% of childhood gastroenteritis are caused by rotaviruses • IgA controls infection and provides immunity of differential durability • Treatment and control • Treatment is replacement of fluids and electrolytes • Vaccine licensed in US in 1998 but was withdrawn because of bowel obstructions in some children • New vaccine has recently been approved

8. Caliciviruses • Gastroenteritis • Norwalk virus and Norwalk-like viruses • Recently infamous for cruise ship infections • Extremely difficult to decontaminate • Unculturable (propagated in animals) • Family Caliciviridae • Clinical Findings and Laboratory Diagnosis • Diarrhea • No defined demographic distribution • In the absence of bacterial etiology, such diarrheal disease is presumed a calicivirus • Diagnosic is by PCR • Epidemiology and Immunity • Clustered outbreaks • Food and water-borne • Communicable • Immunity is not durable

9. Other Reoviradae Members • Orbiviruses • Naturally infect insects • Can be transmitted to vertebrates • Problem in livestock industries • Bluetongue virus of sheep • African horse sickness • Astroviruses • Single-stranded plus sense RNA • Diarrhea • Children and institutionalized elderly • Can establish persistent infection in immunocompromised