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
Genome:Genome: 8 fragments of –ss RNA8 fragments of –ss RNA
Replication:Replication: EndocytosisEndocytosis Nucleus Nucleus Budding Budding
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 drift: EpidemicsAntigenic drift: Epidemics• AnnualAnnual
• Inf. A & BInf. A & B
• Mutation (Deletion and insertionMutation (Deletion and insertion
• Incomplete changeIncomplete change
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