Avian Influenza Bioinformatics Workshop Summer 2006 Avian Influenza • The history of human influenza • The Spanish flu pandemic of 1918 • Emergence of ‘Bird Flu’ (avian influenza) • Phylogenetic comparison of flu sequences • Can bioinformatics prevent the next flu pandemic, or at least provide a warning? – Problem based bioinformatics exercise A Sense of Urgency Bioinformatics Questions 1. Can flu viruses be compared? 2. Which flu genes are important? 3. Where are those data organized? 4. How do you compare viral strains? 5. How do you interpret these results? • (Yes; HA, NA, PB1; NCBI and flu databases; MSA sequence alignment and phylogenetics) • (Compare alignments and addition / loss of aa residues with pathogenicity and epidemiology) Influenza A Up Close and Personal SEM images of Influenza A virus – segmented genome is visible Influenza A Genome Influenza A viral particle structure showing the two key genes, hemagglutinin HA and neuraminidase NA, used for attaching and release Influenza A Genome Influenza - An Emerging Disease Because all known influenza A subtypes exist in the aquatic bird reservoir, influenza is not an eradicable disease; prevention and control are the only realistic goals. If people, pigs, and aquatic birds are the principal variables associated with interspecies transfer of influenza virus and the emergence of new human pandemic strains, influenza surveillance in these species is indicated. Live-bird markets housing a wide variety of avian species together (chickens, ducks, geese, pigeon, turkeys, pheasants, guinea fowl), occasionally with pigs, for sale directly to the public provide outstanding conditions for genetic mixing and spreading of influenza viruses; therefore, these birds should be monitored for influenza viruses. Moreover, if pigs are the mixing vessel for influenza viruses, surveillance in this population may also provide an early warning system for humans http://www.cdc.gov/ncidod/eid/vol4no3/webster.htm Ecology of Influenza A HxNy http://www.medicalecology.org/diseases/influenza/influenza.htm [...]... neuraminidase in influenza virus infections Rev Med Virol 2002 May-Jun; 12 (3): 159-66 Genetic Reassortment Leading to Pandemic Strains Antigenic shifts in Influenza A are caused by reassortment in pigs Swine – Flu Mixing Vessels • The trachea of pigs possess glycoproteins which can bind both bird / human flu strains • Through RNA reassortment, influenza can obtain genes from both birds and humans • Influenza. .. of HA1/HA2 http://www.cdc.gov/ncidod/eid/vol4no3/webster.htm Emergence of H5N1 Influenza in Hong Kong H5N1 enters domestic birds and then mammals http://www.cdc.gov/ncidod/eid/vol4no3/webster.htm Emergence of H5N1 Influenza in Hong Kong The emergence of H5N1 influenza in Hong Kong It is postulated that a nonpathogenic H5N1 influenza spread from migrating shorebirds to ducks by fecal contamination of... 1918, 1934, 1957, 1968, • Compare avian / human / swine, and the location of the 1918 flu sequences • Results suggest that the 1918 flu was a hybrid (reassortant) of avian / mammal – Probably combined in swine in 1910 – 1915 • Characterization of the 1918 Spanish Influenza NA Neuraminidase Strains Compared Following the Evolution of H5N1 Comparing H5N1 to Other Flu Flu! The Influenza Sequence Database •... based on public flu data • Suggest steps for monitoring / containing the spread of avian influenza into humans Prerequisite Knowledge • Using NCBI – Thorough knowledge of tools / databases • Sequence alignment – MSA and phylogenetics for genes / proteins • Biology Workbench – Upload sequences and perform alignments • Influenza – pathogenicity / epidemiology HA Phylogenetics in Flu Reid, Ann H et al... in Pigs of Influenza A Viruses with Pandemic Potential JOURNAL OF VIROLOGY, Sept 1998, p 7367–7373 Highly Pathogenic H5N1 Note the insertion of the basic residues in HA1 / HA2 http://www.cdc.gov/ncidod/eid/vol4no3/webster.htm Highly Pathogenic H5N1 Molecular changes associated with emergence of a highly pathogenic H5N2 influenza virus in chickens in Mexico In 1994, a nonpathogenic H5N2 influenza virus... Attaching to Host Cells • Flu binds to receptors in the trachea and also in the lungs • Antigenic variable regions determine fit of virus and host cells • Influenza will vary in structure of HA and NA – thus HxNy name H5N1 Life Cycle • • • • H5N1 influenza Attachment Cytokine production Acute respiratory distress syndrome • T cell activation • Viral replication and release (host death) • http://www2.niaid... called ‘antigenic shift’ • It can happen in different ways, one of which is common on farms in Southeast Asia and China http://www2.niaid.nih.gov/Newsroom/FocusOn/Flu04/ Background - Antigenic Shift • Influenza A is a single stranded RNA virus containing 8 RNA gene segments, two of which code for the two antigenic surface proteins, hemagglutinin (HA) and neuraminidase (NA) These proteins are involved . Avian Influenza Bioinformatics Workshop Summer 2006 Avian Influenza • The history of human influenza • The Spanish flu pandemic of 1918 • Emergence of ‘Bird Flu’ (avian influenza) • Phylogenetic. with pathogenicity and epidemiology) Influenza A Up Close and Personal SEM images of Influenza A virus – segmented genome is visible Influenza A Genome Influenza A viral particle structure. used for attaching and release Influenza A Genome Influenza - An Emerging Disease Because all known influenza A subtypes exist in the aquatic bird reservoir, influenza is not an eradicable