Viruses Associated with Gastroenteritis

1. Viruses Associated with Gastroenteritis Ghazi Jamjoom

2. VIRAL AGENTS CAUSINGGASTROENTERITIS Major Viruses Rotavirus Enteric adenoviruses Noroviruses : a. Norwalk-like viruses b. Calicivirus c. Astrovirus

3. Noroviruses Norwalk-like Caliciviruses Astroviruses other viruses viruses

4. Viruses associated with gastroenteritis (cont) : • Other viruses (minor): • Coronaviruses • Parvoviruses • Pestiviruses • Toroviruses

5. ROTAVIRUS FamilyReoviridae Genus Rotavirus

6. ROTAVIRUS • First isolated in 1973 from children with diarrhea • EM identification from duodenal biopsies • Human and animal strains

7. Rotavirus

8. Rotavirus- EM Structure

9. ROTAVIRUS • 60-80nm in size • Non-enveloped virus • Double capsid • EM appearance of a wheel with radiating spokes • Icosahedral symmetry • double stranded (ds) RNA in 11 segments (double – double)

10. ROTAVIRUS- 3D STRUCTURE

11. Outer structural proteins - VP7 and VP4 VP7=glycoprotein VP4=protease-cleaved, P protein, viral hemagglutinin, and forms spikes from the surface Inner core structural proteins VP 1, 2, 3, 6 VP6 is an important antigenic determinant Viral Structural Proteins (VP)

12. Genome is composed of 11 segments of double-stranded RNA, • six structural • coding for proteins • five nonstructural • Seven serological groups have been identified (A-G), three of • which (groups A, B, and C) infect humans .

13. STRUCTURE

14. Gene coding assignment

15. Groups, subgoups, serotypes based on viral capsid proteins 7 Groups (A through G) Group A is the most common and has 2 subgroups 10 human serotypes based on G protein (VP 7) 8 P protein serotypes Classification

16. Electropherotypes mobility of RNA segments by PAGE Used in epidemiologic studies Classification(contd.)

18. Rotavirus - Properties • Virus is stable in the environment • Relatively resistant to handwashing agents • Susceptible to disinfection with 95% ethanol, ‘Lysol’, formalin

19. Pathogenesis • Targeted host cells- mature enterocytes lining the tips of intestinal villi • Intermediate/infective sub-viral particle (ISVP) produced through proteolysis • Enter host cell by endocytosis • Virus replicates in the host cell cytoplasm

20. Replication • mRNA transcription with viral RNA polymerase • Capsid proteins formed • mRNA segments formed, assembled into immature capsid • mRNA replicated to form double stranded RNA genome

21. Histopathology • Mature enterocytes lining the tips of intestinal villi are affected • Villous atrophy and blunting • Death of the mature enterocytes

22. Histopathology

23. Epidemiology - Worldwide • Millions are affected • 600,000-850,000 deaths/year • A major cause of diarrhea-associated hospitalizations • Seroprevalence studies show that antibody is present in most by age 3y.

24. Rotavirus-Worldwide distribution(source- centers for disease control and prevention)

25. Estimated Global Distribution of The 800,000 Annual Deaths Caused By Rotavirus Diarrhea

26. Epidemiology : U.S. • No. of children under 5y. affected ~ 2.7 million • Physician visits per year ~ 500,000 • Hospitalizations per year ~ 50,000 • Deaths per year ~ 20 - 40 • % cases w/ dehydration ~ 1-2.5%

27. Epidemiology • Age- 4mo - 2 yearsProtection of younger infants through transplacental antibody transfer • Asymptomatic infectionsare common, especially in adults • Nosocomial infections • Outbreaks

28. Epidemiology (contd.) • Seasonality Winter months (Nov. through May in US) Gradual spread W to E Year-round in the tropics • Incubation period- thought to be <4 days

29. Epidemiology : U.S.(Source- centers for disease control and prevention)

30. Epidemiology (transmission) • Mainly person to person via fecal-oral route • Fomites • Food and water-borne spread is possible • Spread via respiratory route is speculated

31. Epidemiology (spread) • Contagious from before onset of diarrhea to a few days after end of diarrhea • Large amounts of viral particles are shed in diarrheal stools • Infective dose is only 10-100 pfu

32. EPIDEMIOLOGYDifferences in Groups • Group Ainfections are most common • Group Bhas been associated with outbreaks in adults in China • Group Cis responsible for sporadic cases of diarrhea in infants around the world

33. Clinical Features • Incubation period- thought to be <4 days • Fever- can be high grade (>102F in 30%) • Vomiting, nauseaprecede diarrhea • Diarrhea - usually watery (no blood or leukocytes) - lasts 3-9 days - longer in malnourished and immune deficient indiv. - NEC and hemorrhagic GE seen in neonates

34. Mechanism of diarrhea • Watery diarrhea due to net secretion of intestinal fluid • Activation of the enteric nervous system -possible role of enterotoxin

35. Clinical Features(contd.) • Dehydrationis the main contributor to mortality. • Secondary malabsorptionof lactose and fat, and chronic diarrhea are possible

36. Recovery is usually complete. • However, severe diarrhea without fluid and electrolyte • replacement may result in dehydration and death .

37. Immunological Aspects • Immunoglobulin (Ig) A , in the lumen of the gut immunity • to infection. • Actively or passively acquired antibodies (including antibodies in • colostrum and mothers milk) lessen the severity of disease • but does not consistently prevent reinfection . • Absence of antibody small amounts of virus infection • and diarrhea .

38. Diagnosis • Antigen detection in stool by ELISA, Latex Agglutination (for Group A rotavirus) • EM- non-Group A viruses also • Culture- Group A rotaviruses can be cultured in monkey kidney cells • Serology for epidemiologic studies

39. Treatment and Prevention • Treatment- Supportive - oral, IV rehydration • Prevention- Handwashing and disinfection of surfaces

40. Vaccine • Live tetravalent rhesus-human reassortant vaccine (Rotashield) • Licensed for use in August 1998 • Removed from the market in October 1999 due to risk of intussusception • Cases were seen 3-20 days after vaccination • Approx. 15 cases/1.5 million doses • New vaccine from bovine rotavirus under trial

41. Production of rhesus rotavirus (RRV), human rotavirus (HRV) x rhesus rotavirus (RRV)reassortant quadrivalent vaccine wit VP7 serotype 1, 2, 3, and 4 specificity

42. GASTROENTERITIS DUE TO ENTERIC ADENOVIRUS

43. GASTROENTERITIS DUE TO ADENOVIRUS • Types 40, 41 • Belong to serogroup F • Some cases due to types 31, 3, 7

44. Diarrhea due to Enteric Adenovirus • Age <4 years • Year round • Spread via fecal-oral route

45. Clinical features of Enteric Adenovirus gastroenteritis • Incubation period 3 -10 days • Diarrhea lasts for 10 -14 days • Can also cause intussusception, mesenteric adenitis, appendicitis

46. Diagnosis- Enteric adenoviruses • Isolation requires special media-Graham 293 • ELISA for rapid detection is available

47. HUMAN CALICIVIRUSES

48. Belong to Family Caliciviridae Non-enveloped RNA viruses with ss RNA 27-35 nm in size Contain a single capsid protein HUMAN CALICIVIRUSES(HuCV)

49. HUMAN CALICIVIRUSES • Genomic analysis divides it into 4 groups • Human caliciviruses belong to 2 genera

50. NLV (Norovirus) Norwalk virus Hawaii virus Snow Mountain virus Montgomery county virus Taunton (England) SLV (Sapovirus) Sapporo virus Manchester virus Houston/86 London/92 CLASSIFICATION OF HuCV