INTRODUCTIONINTRODUCTION

• Cause RTI Cause RTI

• Genetic variation (shift and drift)Genetic variation (shift and drift)

• Estimated 40-50 million deaths Estimated 40-50 million deaths worldwide in pandemic of worldwide in pandemic of

1918-19191918-1919

PROPERTIESPROPERTIES

• ClassificationClassification: : - - FamilyFamily:: OrthomyxoviridaeOrthomyxoviridae - - GenusGenus:: Three genera according to matrixThree genera according to matrix

protein and nucleoprotein:protein and nucleoprotein: . Influenza A, & B . Influenza A, & B

A (Human & animal; moderate toA (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)

ORTHOMYXOVIRUSESORTHOMYXOVIRUSES

M protein

helical nucleocapsid (RNA plus NP protein)

HA - hemagglutinin

polymerase complex

lipid bilayer membrane

NA - neuraminidase

MorphologyMorphology

• Helical, 100-200 nm.Helical, 100-200 nm.

• EnvelopedEnveloped

• Proteins:Proteins:

-- Hemagglutinin Hemagglutinin (HA, 80%, 15 subtypes; H1-H15):(HA, 80%, 15 subtypes; H1-H15): Agglutinate RBC, AttachmentAgglutinate RBC, Attachment

-- Neuraminidase (NA, 20%, 9 subtypes; N1-N9): Neuraminidase (NA, 20%, 9 subtypes; N1-N9): Destroy neuraminic (Sialic) acid from the receptorDestroy neuraminic (Sialic) acid from the receptor

protein (Release the virus)protein (Release the virus)

-- M2 protein: Ion channels, protons entryM2 protein: Ion channels, protons entry

- Matrix protein (M): Assembly- Matrix protein (M): Assembly

The HA and NA antigens of influenza

Genome:Genome: 8 fragments of –ss RNA8 fragments of –ss RNA

Replication:Replication: EndocytosisEndocytosis Nucleus Nucleus Budding Budding

Cellular replication of influenza virus

Genetic variationGenetic variationAntigenic shift: PandamicsAntigenic shift: Pandamics• Decade (10 years)Decade (10 years)

• Inf. AInf. A

• Human strain + Animal strainHuman strain + Animal strain

Infect same cellInfect same cell Genetic reassortment Genetic reassortment

• Complete changeComplete change

Antigenic ShiftAntigenic Shift Genetic reassortmentGenetic reassortment

Genetic reassortment with influenza A

Antigenic drift: EpidemicsAntigenic drift: Epidemics• AnnualAnnual

• Inf. A & BInf. A & B

• Mutation (Deletion and insertionMutation (Deletion and insertion

• Incomplete changeIncomplete change

Antigenic DriftAntigenic Drift (Mutation)(Mutation)

Antigenic shift and driftAntigenic shift and drift

Pandemics and Pandemic Pandemics and Pandemic Threats of the 20Threats of the 20thth Century Century

• 1918-19 “Spanish flu”1918-19 “Spanish flu” H1N1H1N1• 1957 “Asian flu” 1957 “Asian flu” H2N2H2N2• 1968 “Hong Kong flu”1968 “Hong Kong flu” H3N2H3N2• 1976 “Swine flu” episode1976 “Swine flu” episode H1N1H1N1• 1977 “Russian flu”1977 “Russian flu” H1N1H1N1• 1997 “Bird flu” in HK1997 “Bird flu” in HK H5N1H5N1• 1999 “Bird flu” in HK1999 “Bird flu” in HK H9N2H9N2• 2003 “Bird flu” in Netherlands H7N72003 “Bird flu” in Netherlands H7N7• 2004 “Bird flu” in SE Asia2004 “Bird flu” in SE Asia H5N1H5N1

CLINICAL ASPECTSCLINICAL ASPECTS

• Incubation period:Incubation period: 2-3 days

• Symptoms:Symptoms: Shivering, malaise, headache, aching,

rise T

PATHOGENESISPATHOGENESISDroplets Droplets URT URT Multiply in epith. cellsMultiply in epith. cells Destroy cilia Destroy cilia

• Decreased clearanceDecreased clearance• Risk bacterial infectionRisk bacterial infection• Viremia rareViremia rare

• Secondary bacterial infection:Secondary bacterial infection: - - S. aureusS. aureus - - S. pneumonia, H. influenza, S. pneumonia, H. influenza, and and

hemolytic hemolytic streptococcusstreptococcus

• Complication ( Rey`s syndrome):Complication ( Rey`s syndrome): Often type B: Often type B: - Encephalitis- Encephalitis

- Liver & Viscera- Liver & VisceraFATALFATAL

IMMUNE RESPONSEIMMUNE RESPONSE

• Humoral:Humoral: Is not important Is not important

• Cellular:Cellular: TC cells & Macrophages TC cells & Macrophages

Vaccines:Vaccines: • Killed or inactivated (Inf. A & B):Killed or inactivated (Inf. A & B):

- Whole virus: Local reaction- Whole virus: Local reaction

- Split: Less local reaction- Split: Less local reaction

- Subunit or surface antigen: - Subunit or surface antigen: SaveSave

• Live attenuated:Live attenuated: Adapted to grow at Adapted to grow at lessless

Temp. e,g., 25Temp. e,g., 25oo C C

• Reassortment genes:Reassortment genes: Under test Under test

Subunit influenza vaccine