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MYXOVIRUSES

MYXOVIRUSES. Dr. Nehal Draz. Myxo = affinity to mucin. Myxoviruses. Paramyxo viruses. Orthomyxo viruses. Smaller Segmented RNA genome Liable to Agic variation. Larger Single piece of RNA Not liable to Agic variation. - Parainfluenza - Mumps vairus - Measles virus

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MYXOVIRUSES

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  1. MYXOVIRUSES Dr. Nehal Draz

  2. Myxo = affinity to mucin Myxoviruses Paramyxo viruses Orthomyxo viruses • Smaller • Segmented RNA genome • Liable to Agic variation • Larger • Single piece of RNA • Not liable to Agic variation - Parainfluenza - Mumps vairus - Measles virus - Respiratory syncytial virus Influenza viruses

  3. Influenza Viruses • Replicate in mucus membranes • Target tissue: upper & lower respiratory tract • Cause influenza: acute respiratory disease that may occur in epidemics or even pandemics

  4. Structure • -ve sense ssRNA viruses with segmented genome(8 pieces) • RNA segments + nucleoprotein form a nucleocapsid • RNA segments+ nucleocapsid = a nucleocapsid with helical symmetry

  5. Antigenic structure& Classification I- Type Specific Ag ( core Ag): • Three serotypes: A,B&C according to internal structure ptns ( nucleocapsid & matrix). These ptns don’t cross react II- Strain ( subtype) specific Ag: • Two surface glycoptns, HA&NA are used to subtype the virus • Influenza strains are named after their types of HA& NA surface ptns e.g. H1N1

  6. Haemagglutinin • Binds to host cell surface receptor • The target of neutralizing Abs • Haemagglutinates RBCs from various animal species Neuraminidase • Cleaves neuraminic acid to release virus progeny from infected cells • Degrades the protective layer of mucin in the respiratory tract • Plays a min role in immunity to influenza

  7. Neuraminidase Cleaves neuraminic acid to release virus progeny from infected cells Haemagglutinin Binds to host cell surface receptor

  8. Types of Influenza virus I- Type A virus: • Infects humans as well as animals • Undergoes continuous Agic variations • Many animal species have their own influenza A virus • Pigs & birds are important animal reservoirs playing a role in occurrence of influenza epidemics

  9. II- Type B virus: • causes milder disease • Infects human only • Undergoes Agic variation but only Agic shift III- Type C virus: • Of doubtful pathogenicity • Agically stable

  10. Antigenic Variation1- antigenic shift • It is the process in which the genetic segment encoding for envelope glycoproteinacs (HA&NA) is replaced by another one from a different strain through genetic reassortment causing replacement of the original HA or NA by a new one • Genetic reassortment: the exchange of genetic material between viruses inside a host cell

  11. This is responsible for appearance of completely new strains to which no one is immune & not covered by annual vaccinations Chicken H5N1 Human H3N2 H5N2 influenza A

  12. Agic shift occurs only in infuenza A because it has a wide host range, giving influenza A the opportunity for a major reorganization of its genome & hence its surface Ags • Pigs are susceptible to avian, human & swine influenza viruses and they potentially may be infected with influenza viruses from different species. If this happens, it is possible for the genes of these viruses to mix and create a new virus

  13. Antigenic Variation2- antigenic drift • It is spontaneous point mutation of known strains of influenza causing minor change of an amino acid sequence of HA or NA. • Occurs in influenza A & B

  14. Mode of transmission • Highly contagious disease with person to person transmission • Three modes of transmission Droplet Air- Borne Contact Direct Indirect

  15. Pathogenesis Viral NA degrades the protective mucin layer Allowing the virus to enter the cells Replication inside the cells Cilia damage Epithelial desquamation Epithelial cells of respiratory tract The infection is limited to the respiratory tract….why? There are proteases there essential for HA to be active Despite systemic symptoms, no viremia….why? Those symptoms are due to cytokines

  16. Clinical pictureIncubation period: 1-4 days FEVER Sore throat • . cough Complications headache • pneumonia and respiratory failure • Reye,s Syndrome diarrhea vomiting 50% of infected people don’t present any symptoms But still contagious This makes it difficult to stop the spread of the disease

  17. Reye’s Syndrome • Acute encephalopathy with hepatic necrosis in children & adolescents (2-16 yrs) • A rare complication of influenza A, B and Varicella- Zoster infection • There is an association between salicylate intake and subsequent development of Reye’s Syndrome

  18. Laboratory Diagnosis • Specimen: nasal washings, gargles, throat swabs 1- Direct Virus Demonstration: • Direct Immunofluorescence: for rapid Ag detection in nasal aspirates, not very sensitive • RT-PCR: for detection of viral RNA

  19. 2- Viral Isolation: specimens are inoculated into emberyonated eggs or primary monkey tissue culture • Cell culture are tested for the virus by Haemagglutination

  20. Prophylaxis I-vaccines • Inactivated • Live attenuated • Amantadine& Rimantadine • Zanamavir & Osteomavir II- chemoprophylaxis

  21. I- Influenza vaccines • A new vaccine is formulated annually using the types & strains of influenza predicted to be the major problem for that year. • Predictions are based on world wide monitoring of influenza • The vaccine is multivalent 1) Inactivated vaccine: • Whole killed vaccine prepared in chick embryo • Recommended for persons at increased risk for influenza related complications & their contacts

  22. Given by intramuscular injection • It has a short lived protective effect so usually given in the fall, for the protection to be high in December & January • Given every year as protection is short lived, and also as the most effective strains for the vaccine will change due to shift or drift

  23. 2) Live attenuated • Recently approved only for healthy individuals • Prepared from temperature- sensitive mutants that can replicate in cooler nasal passages (33C) but not in warm lower respiratory tract • Given by nasal spray thus could provide mucosal, humoral & cell-mediated immunity

  24. II- Chemoprophylaxis 1)Amantadine & Rimantadipne: • Prevent penetration & uncoating of the virus • Treat & prevent influenza A only • Given to high risk groups 2) Zanamavir & Oseltamivir (tamiflu) • They are neuraminidase inhibitors, inhibiting the release of virus from infected cells • This limits the infection by reducing the spread of virus from one cell to another • For treatment not prevention • Effective against influenza A &B

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