Microbiology, virology, immunology department

1. Microbiology, virology, immunology department RNA-VIRUSES:PICORNAVIRUSES ORTHOMYXOVIRUSES PARAMYXOVIRUSESCAUSATIVE AGENTS OF HEPATITIS VIRUS

2. PICORNAVIRUSES

3. Genera of Picornaviruses

4. 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

6. Clinical Picornavirus Syndromes

9. * Reclassification of coxsackievirus A23 as echovirus 9, echovirus 8 as 1, echovirus 10 as reovirus, echovirus 28 as rhinovirus type 1A, and echovirus 34 as coxsackievirus A24.

10. Properties of enteroviruses

11. Properties of enteroviruses 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. RNA

12. POLIOMYELITIS Picornavirus • 3 types: Poliovirus 1,2,3 • 30 nm in size

14. Cultivation. SPE. 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 is attended by destruction and the formation of granules in the infected cells.

16. Pathogenesis • Source of infection:Apparent and subclinical patients • Incubation:is usually 7-14 days, but it may rangefrom 3 to 35 days.

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

18. Pathogenesis 1. The mouth is the portal of entry of the virus. 2. The virus first multiplies in the tonsils, the lymph nodes of the neck, Peyer's patches, and the small intestine. 3. Viremia 4.The central nervous system may then be invaded by way of the circulating blood. 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. The anterior horn cells of the spinal cord are most prominently involved.

20. Clinical Findings.When an individual susceptible to infection is exposed to the virus, one of the following responses may occur: • inapparent infection without symptoms (asymptomatic illness), the minor illness – 90% infected people • aseptic meningitis – 1%-2% of patients with poliovirus infections, • paralytic poliomyelitis, the major illness0.1% to 2% of persons with poliovirus • Only about 1% of infections are recognized clinically.

21. Abortive Poliomyelitis. This is the commonest form of the disease. The patient has only the minor illness, characterized by fever, malaise, drowsiness, headache, nausea, vomiting, constipation, and sore throat in various combinations. The patient recovers in a few days. The diagnosis of abortive poliomyelitis can be made only when the virus is isolated or antibody development is measured.

22. Nonparalytic Poliomyelitis (Aseptic Meningitis).In addition to the above symptoms and signs, the patient with the nonparalytic form presents stiffness and pain in the back and neck. The disease lasts 2-10 days, and recovery is rapid and complete. In a small percentage of cases, the disease advances to paralysis.

23. Paralytic Poliomyelitis. The major illness usually follows the minor illness described above, but it may occur without the antecedent first phase. The predominating complaint is flaccid paralysis resulting from lower motor neuron damage. The maximal recovery usually occurs within 6 months, with residual paralysis lasting much longer.

25. Child with polio sequelae

26. Lab Diagnosis • Definitive diagnosis is made by osolation 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 • neutralizing Test • CFT

27. Prevention Both oral polio vaccine (OPV live, attenuated， Sabin, 1957) and inactivated poliovirus vaccine (IPV, Salk, 1954) are avilable IPV is used for adult immunization and Immunocopromised patients

28. COXSACKIEVIRUSES The coxsackieviruses comprise a large subgroup of the enteroviruses. They produce a variety of illnesses in human beings, including aseptic meningitis, herpangina, pleurodynia, hand, foot, and mouth disease, myo- and pericarditis, common colds, and possibly diabetes. Coxsackieviruses have been divided into 2 groups, A and B, having different pathogenic potentials for mice.

29. Group A viruses produce widespread myositis in the skeletal muscles of newborn mice, resulting in flaccid paralysis without other observable lesions. Group Bviruses may produce spasticity effect insucking mice,focal myositis, encephalitis, and, most typically, necrotizing steatitis involving mainly fetal fat lobules. Some B strains also produce pancreatitis, myocarditis, endocarditis, and hepatitis in both suckling and adult mice. Normal adult mice tolerate infections with group B coxsackieviruses.

31. Herpangina: There is an abrupt onset of fever, sore throat, anorexia, dysphagia, vomiting, or abdominal pain. The pharynx is usually hyperaemic, and characteristic discrete vesicles occur on the anterior pillars of the fauces, the palate, uvula, tonsils, or tongue. The illness is self-limited and most frequent in small children.

32. Exanthems – Rubelliform rashes

33. Hand, Foot, and Mouth Disease: The syndrome is characterized by oral and pharyngeal ulcerations and a vesicular rash of the palms and soles that may spread to the arms and legs. Vesicles heal without crusting, which clinically differentiates them from the vesicles of herpes- and pox-viruses. The rare deaths are caused by pneumonia.

34. Hand-foot-and-mouth disease • Hand-foot-and-mouth disease: mostly coxackie A • fever, malaise, sore throat, vesicles on bucсal mucosa, tongue, hands, feet, buttocks • highly infectious • resolution – 1w

35. ECHOVIRUSES (enteric cytopathogenic human orphan viruses) Not produce diseases in sucking mice, rabbits, or monkeys. Monkey kidney and human embryonated kidney cell culture Aseptic meningitis, febrile illnesses with or without rash, common colds, and acute hemorrhagic conjunctivitis are among the diseases caused by echoviruses.

36. Boston exanthem disease. Rashes are commonest in young children.

37. RHINOVIRUSES Rhinoviruses are isolated commonly from the nose and throat but very rarely from feces. These viruses cause upper respiratory tract infections, including the "common cold."

38. Orthomyxovirus

39. Orthomyxovirus Family The name myxovirus was originally applied to influenza viruses. It meant virus with an affinity for mucins.

40. A model of the influenza virion

41. Types:A, B, C Influenza A: In Birds • 16 H variants • 9 N variants In Humans • 3 H variants (H1, H2, and H3) • 2 N variants (N1 and N2) Subtypes:H1N1, H2N2,H2N3

42. Swine New Reassorted virus Influenza Viruses:Antigenic Shift Human virus Avian virus Avian Reservoir Other mammals?

43. Influenza Viruses:Antigenic Drift • Gradual accumulation of mutations that allow the hemagglutinin to escape neutralizing antibodies (Point mutation in HA gene) • Epidemic strains thought to have changes in three or more antigenic sites

44. Pathogenesis and Pathology The virus enters the respiratory tract in airborne droplets. Viremia is rare. Virus is present in the nasopharynx from 1-2 days before to 1-2 days after onset of symptoms. Inflammation of the upper respiratory tract causes necrosis of the ciliated and goblet cells of the tracheal and bronchial mucosa but does not affect the basal layer of epithelium. Interstitial pneumonia may occur with necrosis of bronchiolar epithelium and may be fatal. The pneumonia is often associated with secondary bacterial invaders: staphylococci, pneumococci, streptococci, and Haemophilus influenzae.

46. Clinical Findings The incubation period is 1 or 2 days. Chills, malaise, fever, muscular aches, prostration, and respiratory symptoms may occur. The fever persists for about 3 days; complications are not common, but pneumonia, myocarditis, pericarditis, and central nervous system complications occur rarely. The latter include encephalomyelitis, polyneuritis, Guillain-Barre syndrome, and Reye's syndrome (see below).

47. Influenza Vaccines • Whole virus vaccine: inactivated virus vaccine grown in embryonated eggs; 70-90% effective in healthy persons <65 years of age, 30-70% in persons ≥65 years • Split virus vaccine: previously associated with fewer systemic reactions among the elderly and children <12 years • Subunit vaccine: composed of H and N • Live, attenutated influenza virus vaccines under development

48. Influenza: Chemoprophylaxis • Amantadine and rimantadine: effective against type A, but not type B, influenza viruses; block the M2 ion channel • 70-90% effective in preventing illness • Administered to individuals at high risk of complications who are vaccinated after outbreak of infection, persons with immune defficiency

49. Influenza: Chemotherapy • Amantadine (adults and children ≥ 1 year) and rimantadine (adults) • Zanamivir and oseltamivir: neuraminidase inhibitors active against both type A and B influenza viruses • Reduce duration of illness by ~1 day when administered within 2 days of the onset of illness (uncomplicated influenza)

50. Laboratory Diagnosis Throat washings or garglings are obtained within 3 days after onset and should be tested at once or stored frozen. Penicillin and streptomycin are added to limit bacterial contamination. For rapid detection of influenza virus in clinical specimens, positive smears from nasal swabs may be demonstrated by specific staining with fluorescein-labeled antibody. Paired sera are used to detect rises in HI, CF, or Nt antibodies.