1
Evolution of Influenza A Evolution of Influenza A
Virus in Wild BirdsVirus in Wild Birds
Robert G. Webster, PhDRobert G. Webster, PhD
Division of VirologyDivision of Virology
Department of Infectious DiseasesDepartment of Infectious Diseases
St. Jude Children’s Research HospitalSt. Jude Children’s Research Hospital
• Point mutations
• Reassortment
• Insertions and deletions
• Recombination
Evolution of Influenza A VirusesEvolution of Influenza A Viruses
H1
H2
H3
H4
H5
H6
H7
H8
H9
H10
H11
H12
H13
H14
H15
H16
Influenza A Influenza A Virus Host Virus Host
RangeRange
•Ducks and shorebirds (waders -- families Charadriidae and Scolopaeidae) are the major reservoirs of influenza viruses.
•Influenza A subtypes H1 – H16 in Eurasia.
•H14, H15, H16 not detected in the Americas.
•Shorebirds in the Americas have a higher percentage of H5, H7, H9 viruses.
•Shorebirds carry influenza viruses North in Spring! (U.S.)
•Wild ducks carry influenza viruses South in the autumn! (U.S.)
•Predominant viruses (H3, H6)show a 2 year periodicity.
•Failure to detect influenza in European waders.
Ecology of Influenza Viruses in Wild BirdsEcology of Influenza Viruses in Wild Birds
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The Ecology of Influenza VirusesThe Ecology of Influenza Viruses
Point 1Point 1--22
••Wild aquatic birds are the natural Wild aquatic birds are the natural
reservoirs of all influenza A viruses in reservoirs of all influenza A viruses in
other speciesother species
••In wild aquatic birds, influenza viruses In wild aquatic birds, influenza viruses
replicate predominately in the replicate predominately in the
intestinal tract and are shed by fecal intestinal tract and are shed by fecal
oral transmission often through wateroral transmission often through water
The Ecology of Influenza VirusesThe Ecology of Influenza Viruses
Point 3Point 3--44
• That there are a limited number of host specific lineages of influenza viruses
• There is geographical separation into Eurasian and American lineages
The Ecology of Influenza VirusesThe Ecology of Influenza Viruses
Point 5Point 5--66
• Influenza viruses in their natural reservoirs are in evolutionary stasis
• Rapid evolution occurs after transfer to new hosts
The Ecology of Influenza VirusesThe Ecology of Influenza Viruses
• Most interspecies transmissions are transitory and do not result in stable lineages
• Intermediate hosts involved in interspecies transmission of avian influenza viruses include pigs, chickens, and quail
Point 7Point 7--88
3
H3
H6
H9
Ecology of InfluenzaEcology of Influenza
• Highly pathogenic H5, H7 influenza viruses from 1970s 2003 were not pathogenic in aquatic birds
Eurasian H2 Viruses in the AmericasEurasian H2 Viruses in the AmericasEmergence of Highly Pathogenic Avian Emergence of Highly Pathogenic Avian
Influenza in Mexico in 1995Influenza in Mexico in 1995
4
The St. Jude Avian Influenza The St. Jude Avian Influenza
Genome ProjectGenome Project
• 413 avian influenza viruses
• “proteotyping” or bar-codes for rapid analysis of
data
�Certain proteins inherited as pairs
• Variation in HA, NA, NS
Obenauer et al 2006Obenauer et al 2006
Reassortment/RecombinationReassortment/Recombination
●Reassortment of gene segments is
rampant, especially HA, NA
● Evidence for homologous
recombination not found
►► a rare eventa rare event
H5N1 is Breaking the “Rules”H5N1 is Breaking the “Rules”
• Direct transmission from wild birds to humans
• High lethality for waterfowl
• Transmission of influenza virus genes from domestic poultry to migratory waterfowl
• Transmission of viruses mainly via the respiratory route
• Increased thermal stability
• Extensive diversity in pathogenicity for waterfowl
• Transmission to felids
• Is highly pathogenic H5N1 endemic in wild waterfowl?
CONTINUED RAPID EVOLUTIONCONTINUED RAPID EVOLUTION
AcknowledgementAcknowledgement
ssSupport: AI95357, NIAID, ALSACSupport: AI95357, NIAID, ALSAC
St. Jude Children’s Research HospitalSt. Jude Children’s Research Hospital
Richard Webby, Elena Govorkova, Erich Hoffmann, Diane Hulse, Richard Webby, Elena Govorkova, Erich Hoffmann, Diane Hulse,
Katharine SturmKatharine Sturm--Ramirez, Aleksandr Lipatov and Ramirez, Aleksandr Lipatov and
The Influenza Support StaffThe Influenza Support Staff
Hong Kong UniversityHong Kong University
Drs. Yi Guan, Malik Peiris, Leo Poon, K.Y. Yuen, Honglin Drs. Yi Guan, Malik Peiris, Leo Poon, K.Y. Yuen, Honglin ChenChen
Influenza Research GroupInfluenza Research Group
Indonesian Ministry of Research & TechnologyIndonesian Ministry of Research & TechnologyDr. Amin SoebandrioDr. Amin Soebandrio
Vietnamese Ministry of Agriculture and Rural Health Vietnamese Ministry of Agriculture and Rural Health
DevelopmentDevelopment
Dr. TD NguyenDr. TD Nguyen
Thailand Bureau of Disease Control and Veterinary ServicesThailand Bureau of Disease Control and Veterinary ServicesDr. Chantanee Dr. Chantanee BuranathaiBuranathai
KasetsartKasetsart University, University, KamphaengsaenKamphaengsaen CampusCampus
Dr. Thaweesak SongsermDr. Thaweesak Songserm
St. Jude Children’s Research Hospital
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