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Pandemic H1N1/2009: Virology update. BY Dr Ahmed Morad Asaad M.B.B.Ch , M.Sc , M.D Associate Professor of Microbiology College of Medicine, Najran University. SWINE FLU. Swine flu. Disclaimer: This is JUST FLU !. SWINE FLU paranoia gets out of hands.
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Pandemic H1N1/2009: Virology update BY Dr Ahmed MoradAsaadM.B.B.Ch, M.Sc, M.D Associate Professor of Microbiology College of Medicine, Najran University
SWINE FLU Swine flu
Disclaimer: This is JUST FLU! SWINE FLU paranoia gets out of hands
Influenza viruses • Classified into types A, B, and C • Types A and B cause significant disease worldwide • Types B and C limited to humans • Type A viruses • More virulent • Wild waterfowl reservoir • Affect many species
Influenza viruses • Members of Orthomyxoviruses family • A single-stranded negative-sense segmented RNA genome Host cell Non-infectious genome Host cell ribosomes RNA-dependant RNA polymerase
Influenza viruses • Members of Orthomyxoviruses family • A single-stranded negative-sense segmented RNA genome Host cell Non-infectious genome Host cell ribosomes RNA-dependant RNA polymerase
Influenza A virus • Pleomorphic enveloped particles 120 nm with spike-like projections C. Goldsmith and A. Balish 2009 • 2 glycoproteins: • Haemagglutinin (H): H1 - H16 • Neuraminidase (N): N1 - N9 • Influenza A subtypes according to combinations of HN types. 144 possible subtypes (16×9). H N C. Goldsmith, 2005
Nomenclature Virus type Type of animal Geographic origin Strain number Year of isolation Virus subtype
Influenza A virus genome - 8 segments - 10 functional proteins Hilleman MR, Vaccine, 3068 – 3087 (2004)
HA NA 1 2 3 4 5 6 7 8 RNA gene segments
Antigenic drift • Point mutations in H and/or N • Minor gradual antigenic changes in H & N • Drift mutants will prevail by selective pressure for 2 -5 years PB2 PB1 PA HA HA NP NA NA M1 M2 NS
Antigenic shift • Rearrangement of viral gene segments in cells infected with 2 different viruses (REASSORTMENT) 256 (28) new viruses
Pandemic influenza: The making of a pandemic • A NEW VIRUS Emerges • It causes illness in Humans • It is passes easily person to person • Outbreaks appear worldwide
Emergence of pandemic influenza viruses H3N2 G Neumann et al.Nature, 1-9 (2009) doi:10.1038/nature08157
Genesis of swine-origin H1N1 influenza viruses G Neumann et al.Nature, 1-9 (2009)
H1N1/2009 PB1 PB2 PA H1 NP NS N1 M CDC’s description: “Quadruple” reassortants
H1N1/09 virus: Virulence and pathogenicity Influenza virus host specificity: Haemagglutinin receptor binding specificity (human or avian type receptors) 1 Haemagglutinin cleavage protein: Essential for viral infectivity by mediating fusion between viral envelope and endosomal membrane 2
H1N1/09 virus: Virulence and pathogenicity PB2 protein: Essential for replication of genomic RNA 3 PB1-F2 protein: Induces apoptosis in macrophages, thus down regulating host immune response 4 NS1 protein: Inhibit host interferone 5
H1N1/09 virus: Virulence and pathogenicity • There is a great concern of further mutations (antigenic drift) of the virus which may change its virulence and pathogenicity dramatically .
Seasonal and Pandemic flu vaccines The flu shot vaccine: - Inactivated vaccine (killed virus) - I.M. - People older than 6 months of age The nasal-spray flu vaccine: - Live attenuated virus - Nasal spray - People 2 – 49 years (Not pregnant)
The approved list of vaccines and manufacturers for novel H1N1 influenza: France Australia Switzerland USA
Pandemic flu vaccines: Concerns & Issues • No long-term safety testing for: • Carcinogenesis • Mutagenesis • Fertility impairment
Pandemic flu vaccines: Concerns & Issues Clinical data at the time when pandemic vaccines are first administered will inevitably be limited. Further testing of safety and effectiveness will need to take place after administration of the vaccine has begun. 8 May 2009
“Knowledge is vaccine for swine flu” German Influenza Team For swine flu Paranoia