2. INTRODUCTION Cause RTI Cause RTI Genetic variation (shift and drift) Genetic variation (shift and drift) Estimated 40-50 million deaths worldwide in pandemic of Estimated 40-50 million deaths worldwide in pandemic of1918-1919

3. PROPERTIES Classification: Classification: - Family:Orthomyxoviridae - Genus:Three genera according to matrix protein and nucleoprotein:. Influenza A, & B protein and nucleoprotein:. Influenza A, & B A (Human & animal; moderate to A (Human & animal; moderate to severe illness, shift and drift) severe illness, shift and drift) B ( Human, milder illness, only drift) B ( Human, milder illness, only drift). Influenza C (Animal, rarely human). Influenza C (Animal, rarely human). ‘thogoto-like-viruses’ (Animal). ‘thogoto-like-viruses’ (Animal)

4. ORTHOMYXOVIRUSES ORTHOMYXOVIRUSES M protein helical nucleocapsid (RNA plus NP protein) HA - hemagglutinin polymerase complex lipid bilayer membrane NA - neuraminidase

5. Morphology H Helical, 100-200 nm. E Enveloped P 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

6. The HA and NA antigens of influenza

7. Genome: 8 fragments of –ss RNA Replication: Endocytosis Nucleus Budding

8. Cellular replication of influenza virus

9. Genetic variation Antigenic shift: Pandamics D Decade (10 years) I Inf. A H Human strain + Animal strain Infect same cell Genetic reassortment Complete change

10. Antigenic Shift Genetic reassortment Antigenic Shift Genetic reassortment

11. Genetic reassortment with influenza A

12. Antigenic drift: Epidemics Annual Inf. A & B Mutation (Deletion and insertion Incomplete change

13. Antigenic Drift (Mutation) Antigenic Drift (Mutation)

14. Antigenic shift and drift

15. Pandemics and Pandemic Threats of the 20 th Century 1918-19 “Spanish flu”H1N1 1918-19 “Spanish flu”H1N1 1957 “Asian flu” H2N2 1957 “Asian flu” H2N2 1968 “Hong Kong flu”H3N2 1968 “Hong Kong flu”H3N2 1976 “Swine flu” episodeH1N1 1976 “Swine flu” episodeH1N1 1977 “Russian flu”H1N1 1977 “Russian flu”H1N1 1997 “Bird flu” in HKH5N1 1997 “Bird flu” in HKH5N1 1999 “Bird flu” in HKH9N2 1999 “Bird flu” in HKH9N2 2003 “Bird flu” in Netherlands H7N7 2003 “Bird flu” in Netherlands H7N7 2004 “Bird flu” in SE AsiaH5N1 2004 “Bird flu” in SE AsiaH5N1

16. CLINICAL ASPECTS Incubation period: 2-3 days S Symptoms: Shivering, malaise, headache, aching, rise T

17. PATHOGENESIS Droplets URT Multiply in epith. cells Destroy cilia Decreased clearance Decreased clearance Risk bacterial infection Risk bacterial infection Viremia rare Viremia rare

18. S econdary bacterial infection: - S. aureus - S. pneumonia, H. influenza, and hemolytic streptococcus C Complication ( Rey`s syndrome): Often type B: - Encephalitis - Liver & Viscera FATAL

19. IMMUNE RESPONSE H Humoral: Is not important C Cellular: TC cells & Macrophages

20. 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

21. Subunit influenza vaccine