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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

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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