Transcript MYXOVIRUSES
Dr. Nehal Draz Myxo = affinity to mucin Myxoviruses Orthomyxo viruses -Smaller -Segmented RNA genome -Liable to Agic variation Influenza viruses Paramyxo viruses -Larger -Single piece of RNA - Not liable to Agic variation - Parainfluenza - Mumps vairus - Measles virus - Respiratory syncytial virus Replicate in mucus membranes Target tissue: upper & lower respiratory tract Cause influenza: acute respiratory disease that may occur in epidemics or even pandemics -ve sense ssRNA viruses with segmented genome(8 pieces) RNA segments + nucleoprotein form a nucleocapsid RNA segments+ nucleocapsid = a nucleocapsid with helical symmetry 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 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 Neuraminidase Cleaves neuraminic acid to release virus progeny from infected cells Haemagglutinin Binds to host cell surface receptor 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 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 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 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 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 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 Highly contagious disease with person to person transmission Three modes of transmission Droplet Air- Borne Contact Direct Indirect Viral NA degrades the protective mucin layer Allowing the virus to enter the cells Epithelial cells of respiratory tract Replication inside the cells Cilia damage Epithelial desquamation 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 . FEVER Complications • • pneumonia and respiratory failure Reye,s Syndrome Sore throat cough headache 50% of infected people don’t present any symptoms But still contagious This makes it difficult to stop the spread of the disease 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 Specimen: nasal washings, gargles, throat swabs 1- Direct Virus Demonstration: a) Direct Immunofluorescence: for rapid Ag detection in nasal aspirates, not very sensitive b) RT-PCR: for detection of viral RNA 2- Viral Isolation: specimens are inoculated into emberyonated eggs or primary monkey tissue culture Cell culture are tested for the virus by Haemagglutination I-vaccines - Inactivated - Live attenuated -Amantadine& Rimantadine -Zanamavir & Osteomavir II- chemoprophylaxis 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 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 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 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