1. Viruses associated with gastrointestial tract infections Medical Virology Lecture 03/04 Youjun Feng Center for Infection & Immunity, Zhejiang University School of Medicine fengyj@zju.edu.cn Enterovirus of picornaviridae & acute gastroenterities virus

2. Viruses infected through gastrointestinal tract Enteroviruses of picornaviridae Acute gastroenteritis viruses Polioviruses Coxsackieviruses Echoviruses New enteroviruses Parenteral disease Rotavirus Calicivilus  Norovirus  Sapovirus Astrovirus Enteric adenovirus Viral gastroenteritis/viral diarrhea

3. Enterovirus of picornaviridae

4. PICORNAVIRUSES Small RNA Viruses icosahedral symmetry Non-enveloped + strand RNA + Strand RNA is infectious, serves as mRNA Most are very cytolytic to cells

5. Members Enterovirus Virus Poliovirus Disease Poliomyelitis Rhinovirus Heparnavirus Coxsackie Virus A Coxsackie B Echovirus other Enterovirus 100 serotypes Hepatitis A virus Herpangina, Hand Foot and Mouth disease Myocarditis, Pericarditis Common Cold Hepatitis PICORNAVIRUSES

6. Enterovirus of picornaviridae parenteral disease

7. DISEASE MECHANISMS Transmission route: Fecal-oral Season: summer

8. Viremia DISEASE MECHANISMS

9. Enterovirus of picornaviridae Poliovirus

10. Disease Poliomyelitis Herpangina, Hand Foot and Mouth disease Myocarditis, Pericarditis Serotypes 1-3 1-22, 24 1-6 1-9, 11-27, 29-34 Members Poliovirus Coxsackie Virus A Coxsackie B Echovirus other Enterovirus

11. Poliovirus & poliomyelitis

12. In spinal paralysis one or more limbs may be affected or complete flaccid paralysis may occur. In bulbar paralysis cranial nerves and the respiratory center in the medulla are affected leading to paralysis of neck and respiratory muscles. no sensory loss Iron lung

13. Polio vaccines

14. Decline in Poliomyelitis

15. World Polio Map

18. In 2011, only four countries (Afghanistan, India, Nigeria and Pakistan) remain polio-endemic, down from more than 125 in 1988. Current situation In 2012, only three countries (Afghanistan, Nigeria and Pakistan) remain polio-endemic, down from more than 125 in 1988.

19. Current situation http://www.who.int/csr/don/2011_09_01/en/index.html

20. Enterovirus of picornaviridae Coxsackieviruses Echoviruses &New Enteroviruses

21. Other enteroviruses & diseases

22. PATHOGENESIS Fecal-Oral route trasmission Spread in the body like polioviruses Disease Associations Paralytic Disease Meningitis Enc ephalitis Undifferentiated febrile illness Hand foot mouth disease. Herpangina Epidemic Pleurodynia (Bornholm disease) Myocarditis Respiratory Infections Rubelliform rashes. Neonatal Infection Conjunctivitis Pancreatitis/Diabetes

23. Exanthems - Rubelliform rashes - EV leading cause in summer & fall. All types of rash

24. Herpangina – usually coxackie A acute onset, fever, sore throat, dysphagia lesions – posterior pharynx no gingivitis Herpangina/

25. Hand-foot-and-mouth disease: mostly coxackie A 14, HEV71 – fever, malaise, sore throat, vesicles on bucal mucosa, tongue, hands, feet, buttocks highly infectious resolution – 1w Hand-foot-and-mouth disease Hand food and mouth disease(HFMD) Typical lesions around the Mouth of an 11 month old male

26. Management and Prevention no specific antiviral therapy available no vaccine available mainly because of the multiplicity of serotypes

27. Viruses infected through gastrointestinal tract Enteroviruses of picornaviridae Acute gastroenteritis viruses Polioviruses Coxsackieviruses Echoviruses New enteroviruses parenteral disease Rotavirus Calicivilus  Norovirus  sapovirus Astrovirus Enteric adenovirus viral gastroenteritis/viral diarrhea

28. Viruses infected through gastrointestinal tract rotavirus

32. Rotavirus Pathogenesis Universal disease – All children are exposed and acquire antibodies by age 5 Leading cause of severe dehydrating diarrhea in infants and young children Sudden onset of watery diarrhea, fever and vomiting Recovery in 4-5 days

34. Rotavirus Transmission Fecal-oral? – Improvements in water, sanitation, hygiene have not decreased incidence

35. Diagnosis Rapid diagnosis - antigen detection in stool by ELISA (uses a monoclonal antibody). Electron microscopy

36. Rotavirus vaccines Wyeth - Rotashield (Sept. 1998) – Live, oral, tetravalent – human/simian re-assortant viruses – withdrawn in 1999 due to increased incidence of intus-susception Merck - Rotateq (Feb. 2006) – Live, oral, penta-valent – Bovine/human re-assortant viruses

37. Rotavirus vaccines GSK - Rotarix; not yet available in U.S. – Live, oral, attenuated, human – Mono-valent – Cross-protective, replicates well in GI

38. Treatment Supportive - rehydration (oral / intravenous) Antiviral agents not known to be effective Treatment and prevention Prevention of spread Hand washing with good technique Disinfection of surfaces, toilets, toys

40. First discovered in Norwalk, Ohio Has been at the root of several epidemics or outbreaks of gastroenteritis across North America in hospital emergency rooms, schools and even on cruise ships There is a group of similar or related viruses that are referred to as Norwalk-like viruses or agents. Norwalk virus Can infect people of any age and usually cause profuse watery diarrhea, vomiting and fatigue. The infection lasts a few days and there is no specific treatment. Most of the time, it spreads form one person to another through direct or indirect contact with infected feces or vomit. The infection develops within 1-2 days after contact with an infected person.

45. SUMMARY 1. Know the common viruses infected through gastrointestial tract: Enterovirus of picornaviridae and acute gastroenteritis virus. 2. Understand the properties of picornaviruses. 3. Master the clinical findings as a result of rotavirus infection.

46. 1.Each of the following statements regarding rotavirus is correct EXCEPT: (A)the infection mainly affects children younger than 3 years (B)it is a major cause of death in children in developing countries (C)a high viral concentration is necessary for a efficient transfer of the virus (D)in the northern hemisphere the virus is transmitted during the winter/spring season Self control questions 2.Each of the following statements regarding norovirus is correct EXCEPT: (A)the infection mainly affects younger children and older people as well (B)epidemics occur every 2 to 3 years (C)the first line diagnostics is the detection of the virus by PCR from fecal samples (D)a vaccine is available that protects people from norovirus infection

47. 3. Each of the following statements regarding the mode of action of the viruses/bacteria is correct EXCEPT: A. noroviruses possess an enzyme that inhibits proteinsynthesis of the host cell B. rotaviruses induce cell death (apoptosis) thereby causing diarrhea C. Shigella produces a N-glycosidase that has a specificity for 28S ribosomal RNA and upon this action stops protein synthesis of the host cell D. Vibrio cholerae ADP-ribosylates G-proteins and thereby activates an adenylate cyclase which indirectly affects the efflux of water 4. Each of the following statements regarding the treatment of severe diarrhea is correct EXCEPT: A. if possible glucose should be given the oral way at a concentration of 20g/L B. Chloride and bicarbonate losses should be included in the glucose/electrolyte solution to compensate anionic loss C. sodium and potassium losses should be included in the glucose/electrolyte solution to compensate cationic loss D. coca cola contains all the electrolytes and the glucose to compensate the loss of glucose and electrolytes that are lost during diarrhea

48. 6. Please describe the general properties of picornaviruses. 7. What are the clinical findings as a result of rotavirus infection versus Norwalk virus infection? 8. What causes poliomyelitis? What is the route of infection? What is the global situation of the disease? How about the vaccine? A. noroviruses have an infectious dose lower than 100 particles B. rotaviruses have an infectious dose higher than 1000 particles C. campylobacter requires 1000 to 10.000 particles to become infective D. Vibrio cholerae requires > 1.000.000 particles to become infective 5. Each of the following statements regarding the infectious dose of the viruses/bacteria is correct EXCEPT: