INTRODUCTION Cause RTI Cause RTI Genetic variation (shift and drift) Genetic variation (shift and drift) Estimated million deaths worldwide in pandemic of Estimated million deaths worldwide in pandemic of

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)

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

Morphology H Helical, 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

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 D Decade (10 years) I Inf. A H Human strain + Animal strain Infect same cell Genetic reassortment Complete change

Antigenic Shift Genetic reassortment 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 Drift (Mutation)

Antigenic shift and drift

Pandemics and Pandemic Threats of the 20 th Century “Spanish flu”H1N “Spanish flu”H1N “Asian flu” H2N “Asian flu” H2N “Hong Kong flu”H3N “Hong Kong flu”H3N “Swine flu” episodeH1N “Swine flu” episodeH1N “Russian flu”H1N “Russian flu”H1N “Bird flu” in HKH5N “Bird flu” in HKH5N “Bird flu” in HKH9N “Bird flu” in HKH9N “Bird flu” in Netherlands H7N “Bird flu” in Netherlands H7N “Bird flu” in SE AsiaH5N “Bird flu” in SE AsiaH5N1

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

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

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

IMMUNE RESPONSE H Humoral: Is not important C 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