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Viral Genomics: Strength in Numbers David Spiro Assistant Investigator J. Craig Venter Institute dspiro@jcvi.org. RNA viruses make up the majority of emerging diseases. ssRNA negative strand Orthomyxoviridae: Influenza A Filoviridae: Ebola, Marburg
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Viral Genomics: Strength in NumbersDavid SpiroAssistant Investigator J. Craig Venter Institutedspiro@jcvi.org
RNA viruses make up the majority of emerging diseases • ssRNA negative strand • Orthomyxoviridae: Influenza A • Filoviridae: Ebola, Marburg • Bunyaviridae: Hanta virus, California encephalitis virus • ssRNA positive strand • Coronaviridae: SARS/Cov • Flaviviridae: Dengue, Yellow Fever Virus, West Nile • Herpeviridae: Hepatitis E
Viral Genomics For Better Preparedness • Large datasets to track virus evolution and host shifts (Surveillance programs, Molecular Evolution) 2 Whole genomics approach to detect mutations in entire viral genomes (Focusing beyond surface proteins) 3 New tools for high throughput sequencing and analysis (Laboratory and Computational) 4 Data in public genomic and epidemiological databases (Reporting genetic and phenotypic links)
Influenza A Genome Sequencing Project • Family Orthomyxoviridae • Segmented single-stranded negative RNA genome • HA, NA, NP, M, PB1, PB2, PA, NS • Masters of Host Adaptation: • Rapid viral adaptation requires yearly vaccine development Antigenic drift: High mutation rate HA and NA Selection by host immune system Antigenic shift: Viral meosis- mixing of segments due to coinfection with multiple strains Fields Virology. Third edition. Lippincott Williams and Wilkins, Philadelphia
Seg1 (PB2) Seg2 (PB1) Seg3 (PA) Seg4 (HA) Seg5 (NP) Seg6 (NA) Seg7 (M) Seg8 (NS) 2 RNA preparation 1 Collections 3 150 genomes/month 8 Primer Design NCBI Closure 4 RT-PCR Assembly Tracking Validation 7 5 Sequencing 6
CURRENT AND UPCOMING PROJECTS Alaska 2006-2007 Canada 2006-2007 Italy 1999-2004 Hong Kong 1989-2005 North America 1986-2005 Italy 1986-2005 New York 2002-2006 Afganisan H5N1 Hong Kong 2007-2008 Influenza B 1986-2006 Vietnam H5N1 Nigeria, Niger Cote D’Ivoire Avian H5N1 Egypt H5N1 Mexico Yucatan New Zealand 2002-2006 Cameroon Influenza A Kenya 2003-2005 Australia 2002-2005 Australia 1978-2006 • Avian • Human
Animal Coronavirus Genome Project • Emerging viral threats • Transmission from animal reservoirs to humans • What genomic changes occur when virus changes hosts? SARS/CoV