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Transcript
Reoviruses, Rotaviruses and Caliciviruses Chapter 37 • 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 • • • 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 • • • • 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 • • • • • • Rotavirus Gene Segments Segmen Product t 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 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 • • • • • • 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 • • • • • • • • • • • • • • 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 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 • • • •