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PATH 3610 (104)
Rob Foster (26)
Lecture 9

Lecture 9 notes

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University of Guelph
PATH 3610
Rob Foster

LECTURE 9 - ENTERIC VIRUSES • Gastroenteritis means inflammation of the stomach, small and large intestines • Viruses enter GI tract orally and undergo 1º replication in lymphoid tissue associated with gut leading to 2º systematic spread and disease unrelated to GI portal of entry. • These viruses have little to no ability to disrupt the structure or function of the GI tract • Pathophysiology of GI associated viruses • GI viruses have a tropism for cells in a specific state of differentiation • Viruses that destroy cells on the tip of the villus inhibit the absorptive function of the gut as the surviving epithelium is secretory. These cells are replaced quite rapidly because the cells on the crypt are still intact. • Viral destruction of the crypt epithelium results in failure of renewal of villus absorptive cells and collapse of the villi. Regeneration is a longer process than after viral infections of villous tip epithelium. Causative agents of gastroenteritis in humans and their general characteristics including genome and virion structure Rotaviruses • Group A rotaviruses are a major cause of epidemic diarrheal disease in children • Clinical symptoms: onset is often abrupt, vomiting, watery diarrhea, severe dehydration, fever and abdominal pain occur frequently, malnutrition increases severity of symptoms. • Immunity after infection is incomplete, but repeat infections tend to be less severe than the original infection. Characteristics • Nonenveloped, tripled layered virus (it is very protected from the stomach enzymes) • Icosahedral capsid • Genome composed of segmented double-stranded RNA. • Acid resistant, stable in the environment • Trypsin facilitates viral infectivity (cleaves VP4 to form VP5 and VP8, whih interact with cellular receptors). Rotavirus proteins • RNA 4 – protein VP4 – spike, neutralizing antigen, attachment, fusion, trypsin-enhanced activity, P serotype determinant • RNA 9 – G serotype determinant • RNA 10 – viral endotoxin Classification • 7 antigenically different serogroups • Group A further subdivided into subgroups o Cause of most human disease Epidemiology • The geographical distribution of different human rotavirus strains varie: o P1A[8]G1 – globally predominant o P[6]G9, G5 and G8 are more frequent in India, Brazil and Africa (respectively) • Transmission: o Fecal/oral route – poor hygiene, over-crowding o Common nosocomial infection o Outbreaks are very difficult to control Immunity Rotaviruses induce a mucosal intestinal IgA response which is not generally persistent -> neutralizing IgA against viral proteins preventing viral binding and penetration. Caliciviruses – Norwalk virus - Norwalk virus causes epidemic gastroenteritis in humans - Increasingly being recognized as leading cause of food borne illness – associated with contaminated food or water supplies - Common problem on cruise ships Characteristics • Positive sense single stranded RNA – (+) ssRNA • Non-enveloped icosahedral virus • ORF1 – polyprotein encoding non-structural proteins • ORF2 – capsid protein • ORF3 – cis role in VP1 upregulation and stability - Classified based on the capsid gene sequence – Genogroup I and II - Transmitted primarily fecal-oral route - May be transmitted by aerosols contaminated with vomit from infected individuals - Outbreaks resulting from contamination of water systems have been documented - Highly infectious Clinical symptoms of NV infection - Illness begins suddenly - Severe vomiting, watery diarrhea, nausea, abdominal cramps, fever - Very young, elderly and those immunocompromised may experience more severe symptoms Immunity - May be strain-specific and lasts only a few months - Recent evidence also suggests that susceptibility to infection may be genetically determined – secretors of types O and A are at greatest risk of NV infection and disease. Astroviruses - Like rotaviruses, astrovirus infections occur throughout the year wit
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