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INTRODUCTION • Cause RTI • Genetic variation (shift and drift) • Estimated 40-50 million deaths worldwide in pandemic of 1918-1919 PROPERTIES • Classification: - Family: Orthomyxoviridae - Genus: Three genera according to matrix protein and nucleoprotein: . Influenza A, & B A (Human & animal; moderate to severe illness, shift and drift) B ( Human, milder illness, only drift) . Influenza C (Animal, rarely human) . ‘thogoto-like-viruses’ (Animal) ORTHOMYXOVIRUSES HA - hemagglutinin NA - neuraminidase helical nucleocapsid (RNA plus NP protein) lipid bilayer membrane polymerase complex M protein Morphology • Helical, 100-200 nm. • Enveloped • Proteins: - - Hemagglutinin (HA, 80%, 15 subtypes; H1-H15): Agglutinate RBC, Attachment Neuraminidase (NA, 20%, 9 subtypes; N1-N9): Destroy neuraminic (Sialic) acid from the receptor protein (Release the virus) M2 protein: Ion channels, protons entry Matrix protein (M): Assembly The HA and NA antigens of influenza Genome: 8 fragments of –ss RNA Replication: Endocytosis Nucleus Budding Cellular replication of influenza virus Genetic variation Antigenic shift: Pandamics • • • • Decade (10 years) Inf. A Human strain + Animal strain Infect same cell Genetic reassortment Complete change Antigenic Shift Genetic reassortment Genetic reassortment with influenza A Antigenic drift: Epidemics • • • • Annual Inf. A & B Mutation (Deletion and insertion Incomplete change Antigenic Drift (Mutation) Antigenic shift and drift Pandemics and Pandemic Threats of the 20th Century • • • • • • • • • 1918-19 “Spanish flu” H1N1 1957 “Asian flu” H2N2 1968 “Hong Kong flu” H3N2 1976 “Swine flu” episode H1N1 1977 “Russian flu” H1N1 1997 “Bird flu” in HK H5N1 1999 “Bird flu” in HK H9N2 2003 “Bird flu” in Netherlands H7N7 2004 “Bird flu” in SE Asia H5N1 CLINICAL ASPECTS • • Incubation period: 2-3 days Symptoms: Shivering, malaise, headache, aching, rise T PATHOGENESIS Droplets URT Multiply in epith. cells Destroy cilia • Decreased clearance • Risk bacterial infection • Viremia rare • Secondary bacterial infection: - S. aureus - S. pneumonia, H. influenza, and hemolytic streptococcus • Complication ( Rey`s syndrome): Often type B: - Encephalitis - Liver & Viscera FATAL IMMUNE RESPONSE • • Humoral: Is not important Cellular: TC cells & Macrophages Vaccines: • Killed or inactivated (Inf. A & B): • • - Whole virus: Local reaction - Split: Less local reaction - Subunit or surface antigen: Save Live attenuated: Adapted to grow at less Temp. e,g., 25o C Reassortment genes: Under test Subunit influenza vaccine