Picornaviruses: Poliovirus.

1. Microbiology, virology, immunology department Picornaviruses: Poliovirus.

2. Picornaviruses The name is derived from picomeaning small, and RNA referring to the ribonucleicacid genome, so "picornavirus" literally means small RNA virus.

3. Electron Micrograph of Picornaviruses

4. Properties of picornaviruses +RNA

5. Picornavirus Classification • Picornaviruses are separated into nine distinct genera.

6. Genera of Picornaviruses

7. Picornavirus Classification Three important to humans • Enteroviruses • Rhinoviruses • Hepatitis A Virus

8. Aseptic meningitis Nonspecific febrile illness Colds Conjunctivitis Pharyngitis Herpangina Hepatitis Exanthems Encephalitis Paralytic polio Vomiting Diarrhea Pericarditis Myocarditis Hand-foot-mouth syndrome Clinical manifestation of Enterovirus Infections

9. Pathogenesis of infections Enteroviruscan replicate in epithelium of the nasopharynx and regional lymphoid tissue, conjunctiva, intestines, mesenteric nodes, and the reticuloendothelial system. Viremia may cause virus transfer to the spinal cord, brain, meninges, heart, liver, and skin. Some chronic enterovirus infections result in postviral fatigue syndrome. Rhinoviruses infect and replicate mainly in nasopharyngeal epithelium and regional lymph nodes.

10. "Enteroviruses transmission'

11. Pathogenesis of enterovirus infection Replication in oropharynx Rhino,echo, coxsackie,polio Primary viremia Secondary viremia Target Tissue Skin Muscle Brain Meninges Liver Echo Coxsackie A Echo Coxsackie A, B Polio Coxsackie Echo Polio Coxsackie Echo Coxsackie

12. POLIOVIRUS

13. HISTORICAL ASPECTS • Associated with man since ancient times • Jakob Heine (1840) – first medical report • Karl Oskar Medin (1890) – first epidemic • Karl Landsteiner (1909) – transmission of virus • Jonas Salk (1940s) – inactivated viral vaccine • Sabin (1958) – oral vaccine • 1949 – three serotypes

14. Morphology. The virus is 30 nm in size and forms intranuclear inclusions. The virion is icosahedral and consists ofa single sense-strand RNA and a protein capsid containing 32 spherical subunits (capsomeres). This genome RNA serves as an mRNA and initiates the synthesis of virus macromolecules. The poliomyelitis virus has neither an outer membrane nor lipids and is therefore not sensitive to the effect of ether and sodium desoxycholate.

15. Morphology. 3 types: Poliovirus 1,2,3 Duringepidemic outbreaks, type I is most frequently isolated (in 65-95 per cent of cases) while types II and III account for the remaining 5-35 per cent of cases.

16. Poliomielitis virus

17. The Nobel Prize in Physiology or Medicine 1954 "for their discovery of the ability of poliomyelitis viruses to grow in cultures of various types of tissue" John Franklin Thomas Huckle Frederick Chapman EndersWellerRobbins

18. Cultivation. CPE. The poliomyelitis virus is cultivated on kidney cells of green African monkeys and on diploid human cells devoid of latent SV40 viruses. The cytopathic effect (CPE) is attended by destruction and the formation of granules in the infected cells.

19. CPE of enteroviruses in monkey kidney cells Normal cell culture

20. Resistance. The virus is extremely resistant to photodynamic inactivation. It survives in sterile water at room temperature for a period of more than 100 days, in milk for 90 days, in faeces in the cold for more than 6 months, and in sewage for several months. It withstands exposure to 0.5-1 per cent phenol solutions and remains viable for several weeks at pH 3.8-8.5.

21. Resistance. The poliomyelitis virus is sensitive to calcium chlorate lime, chloramine, formalin, potassium permanganate, and hydrogen peroxide solutions. It is rapidly killed on boiling.

22. Poliomyelitis is an acute infectious disease that in its serious form affects the central nervous system. The destruction of motor neurons in the spinal cord results in flaccid paralysis (less than 0.1%). However, most poliovirus infections are subclinical.

23. Epidemiology Natural infection occurs only in man. • Source of infection:Apparent and subclinical patients • Incubation:is usually 7-14 days, but it may rangefrom 3 to 35 days.

24. Transmission • Fecal – oral route:poor hygiene, dirty diapers (especially in day-care settings) • Ingestion via contaminated food and water • Contact with infected hands • Inhalationof infectious aerosols Commoner in areas of poor sanitation

25. Pathogenesis -1 • The mouth is the portal of entry of the virus. • Following ingestion, the virus multiplies in the oropharyngeal and intestinal mucosa.

26. Pathogenesis-2 • The lymphatic system, in particular the tonsils and the Peyer's patches of the ileum, is invaded and the virus enters the blood resulting in a transient viremia. The virus may be found in the blood of patients with abortive and nonparalytic poliomyelitis. • The central nervous system may then be invaded by way of the circulating blood.

27. Pathogenesis-3 • Poliovirus can spread along axons of peripheral nerves to the central nervous system, and there it continues to progress along the fibers of the lower motor neurons to increasingly involve the spinal cord or the brain: • infects anterior horn cells of motor neurons in spinal cord causing flaccid paralysis. • infects brain causing tissue damage-affects breathing (bulbar polio) • Virus shed in feces

28. Pathogenesis of polio viruses infection Poliovirus can survive and multiply within the blood and lymphatics for 17 weeks

29. Clinical Manifestations Polio infection Inapparent infection Clinical poliomyelitis Abortive polio (minor illness) Involvement of CNS (major illness) Non-paralytic polio Paralytic polio Spinal polio Bulbar polio Bulbospinal polio

30. Outcomes of poliovirus infection

31. Clinical Manifestations Asymptomatic (Subclinical) infection (90 - 95%) - inapparent subclinical infection account for the vast majority of poliovirus infections.

32. Clinical Manifestations Abortive infection (4 - 8%) - a minor influenza-like illness occurs, characterized by fever, malaise, drowsiness, headache, nausea, vomiting, constipation, and sore throat in various combinations. Recovery occurs within a few days and the diagnosis can only be made by the laboratory.

33. Clinical Manifestations Major illness (1 - 2%) - the major illness may present 2 - 3 days following the minor illness or without any preceding minor illness. Signs of aseptic meningitis are common. Involvement of the anterior horn cells lead to flaccid paralysis(0.1% to 2% of persons with poliovirus ). Involvement of the medulla may lead to respiratory paralysisanddeath.

34. Paralytic Poliomyelitis. • resulting from lower motor neuron damage. • Spinal polio - 79% of paralytic cases; • Bulbospinal polio - 19% of paralytic cases; • Bulbar polio - 2% of paralytic cases • The maximal recovery usually occurs within 6 months, with residual paralysis lasting much longer.

35. Egyptian stele from the 18th dynasty showing a victim of polio with a withered leg  

36. Victims of paralytic polio Muscle paralysis can sometimes result in skeletal deformities, tightening of the joints and movement disability.

37. Child with polio sequelae

38. Franklin D. Roosevelt • Born in 1882 at Hyde Park, New York--now a national historic site--he attended Harvard University and Columbia Law School. On St. Patrick's Day, 1905, he married Eleanor Roosevelt. • Following the example of his fifth cousin, President Theodore Roosevelt, whom he greatly admired, Franklin D. Roosevelt entered public service through politics, but as a Democrat. He won election to the New York Senate in 1910. President Wilson appointed him Assistant Secretary of the Navy, and he was the Democratic nominee for Vice President in 1920. • In the summer of 1921, when he was 39, disaster hit-he was stricken with poliomyelitis. Demonstrating indomitable courage, he fought to regain the use of his legs, particularly through swimming. At the 1924 Democratic Convention he dramatically appeared on crutches to nominate Alfred E. Smith as "the Happy Warrior." In 1928 Roosevelt became Governor of New York. • He was elected President in November 1932, to the first of four terms.

39. Polio afflicted everyone socially as well as medically • Franklin Delano Roosevelt • “Once you’ve spent two years trying to wiggle one toe, everything is in proportion.”—Franklin D. Roosevelt, 1945 http://americanhistory.si.edu/polio/howpolio/fdr.htm

40. Immunity • Active immunity: • Life-long, type-specific (is permanent to the type causing the infection) • Mechanism: • Local:sIgA are present in the tonsils and gastrointestinal tract, and are able to block virus replication; • Humoral: IgG and IgM can prevent the spread of the virus to motor neurons of the CNS. • Passive immunity:Maternal antibodies cross the placenta, and protect the infant from polio infection during the first 2-3 months of life.

41. Lab Diagnosis • Definitive diagnosis is made by isolation of the virus from stool, CFS, oropharyngeal secretions • Cell culture involves fibroblastic MRC-5 cells CPE is usually evident within 36 hours • Serotyping is based on neutralization of CPE by standardized antisera using intersecting pool followed by specific sera. • ELISA • IFA • CFT

42. Treatment There is no specific treatment. Treatment involves reduction of pain and muscle spasm and maintenance of respiration and hydration. When the fever subsides, early mobilization and active exercise are begun. There is no role for antiserum.

43. Treatment Early injections of gamma-globulin, blood transfusion, wide use of vitamins C and B,-, amino acids (leucine, glutamic acid), analgesics (analgine, amidopyrine, pantopon, etc.), mediators, and stimulants (proserine, galanthamine, dibazol, etc.) are recommended.

44. Treatment An orthopaedic regimen is set up from the first day that paralysis develops to prevent contractures and deformations, and exercise therapy is carried out during the rehabilitation period. An apparatus for artificial respiration is employed when there are respiration disturbances.

45. Prevention No specific antiviral therapy is available. However the disease may be prevented through vaccination. There are two vaccines available. • oral polio vaccine (OPV live, attenuated， Sabin, 1957) consists of live attenuated virus of all 3 serotypes • inactivated poliovirus vaccine (IPV, Salk, 1954) consists of formalin inactivated virus of all 3 poliovirus serotypes

46. Albert Sabin (1906-1993) 1958

47. Most countries use OPV because of its ability to induce local immunity and also it is much cheaper to produce than IPV. OPV is used for the WHO poliovirus eradication campaign

48. Advantages and disadvantages of OPV Advantages • Effectiveness (The normal response rate to OPV is close to 100%) • Lifelong immunity • Induces both systemic (IgG) and local (IgA) immunity • Induction of secretory antibody response similar to that of natural infection • Ease of administration • Lack of need for repeated boosters • Possibility of attenuated virus circulating in community by spread to contacts (indirect immunization) (herd immunity)

49. Advantages and disadvantages of OPV Rarely causes paralytic poliomyelitis, around 1 in 3 million doses Disadvantages • Can mutate to more virulent strain • Unsafe administration for immunodeficient patients • Risk of vaccine-associated poliomyelites in vaccine recipients or contacts • Spread of vaccine to contacts without their consent • May be blocked if another enterovirus is infecting a cells

50. Jonas Salk 1952