Literature detail

Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck.

Hassan Zaraket¹ Tatiana Baranovich² Bryan S Kaplan² Robert Carter³ Min-Suk Song² James C Paulson⁴ Jerold E Rehg⁵ Justin Bahl⁶ Jeri C Crumpton² Jon Seiler² Michael Edmonson³ Gang Wu³ Erik Karlsson² Thomas Fabrizio² Huachen Zhu⁷ Yi Guan⁷ Matloob Husain⁸ Stacey Schultz-Cherry² Scott Krauss² Ryan McBride⁴ Robert G Webster² Elena A Govorkova² Jinghui Zhang³ Charles J Russell⁹ Richard J Webby⁹

Affiliations 9 institutions

1] Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA [2] Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, PO Box 11-0236 Riad El Solh, Beirut 1107 2020, Lebanon.
Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
Department of Computation Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
Departments of Cell and Molecular Biology and Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, MEM-L71, La Jolla, California 92037, USA.
Department of Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
School of Public Health, The University of Texas Health Science Center at Houston, 1200 Pressler Street, Houston Texas 77030 USA.
Joint Influenza Research Center (Shantou University Medical College &Hong Kong University), Shantou University Medical College, Shantou, Guangdong 515031, PR China.
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
1] Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA [2] Department of Microbiology, Immunology &Biochemistry, College of Medicine, The University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.

PMID 25850788 2015 Nat Commun eng epublish

PubMed DOI Browse context

Article

Publication summary

Human infection with avian influenza A(H7N9) virus is associated mainly with the exposure to infected poultry. The factors that allow interspecies transmission but limit human-to-human transmission are unknown. Here we show that A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. In contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form. Airborne transmission in ferrets is accompanied by the mutations in PB1, NP and NA genes that reduce viral polymerase and neuraminidase activity. Therefore, while A(H7N9) virus can infect mammals, further adaptation appears to incur a fitness cost. Our results reveal that a tight genetic bottleneck during avian-to-mammalian transmission is a limiting factor in A(H7N9) influenza virus adaptation to mammals. This previously unrecognized biological mechanism limiting species jumps provides a measure of adaptive potential and may serve as a risk assessment tool for pandemic preparedness.

Genetic Variation Adaptation, Physiological Animals Asymptomatic Infections Chickens Chlorocebus aethiops Dogs Ferrets HEK293 Cells Humans Influenza A Virus, H7N9 Subtype Influenza in Birds Influenza, Human Madin Darby Canine Kidney Cells Multiplex Polymerase Chain Reaction Mutation Neuraminidase Nucleocapsid Proteins

Structured evidence records

Evidence records

4 total

Cross Species Transmission 1 records

Cross Species Transmission Extraction confidence 0.95

Key finding

Influenza A(H7N9) virus was able to transmit from chickens to ferrets, demonstrating an avian-to-mammalian host jump accompanied by a strong genetic bottleneck.

Virus

Host

Location

Supporting text

A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. In contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form. Our results reveal that a tight genetic bottleneck during avian-to-mammalian transmission is a limiting factor in A(H7N9) influenza virus adaptation to mammals.

Method: infection in chickens; infection in ferrets; genetic analysis
Study design: animal experiment
Transmission direction: animal-to-animal

Genomic Evolution 1 records

Genomic Evolution Extraction confidence 0.88

Key finding

Genomic analysis of influenza A(H7N9) during avian-to-mammalian transmission showed a narrow genetic bottleneck and specific PB1, NP, and NA mutations linked to restricted adaptation in ferrets.

Virus

Host

Location

Supporting text

Airborne transmission in ferrets is accompanied by the mutations in PB1, NP and NA genes that reduce viral polymerase and neuraminidase activity. Our results reveal that a tight genetic bottleneck during avian-to-mammalian transmission is a limiting factor in A(H7N9) influenza virus adaptation to mammals.

Genes or proteins: PB1; NP; NA
Analysis methods: genetic diversity analysis; mutation analysis

Host Range Experiment 1 records

Host Range Experiment Extraction confidence 0.95

Key finding

Experimental infection with A/Anhui/1/2013(H7N9) virus showed asymptomatic infection and high diversity in chickens, but limited diversity and adaptation in ferrets, demonstrating restricted mammalian adaptation.

Virus

Host

Location

Supporting text

Here we show that A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. In contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form.

Method: experimental infection
Experimental system: in vivo animal experiment

Molecular Adaptation 1 records

Molecular Adaptation Extraction confidence 0.98

Key finding

Mutations in PB1, NP, and NA genes of A(H7N9) virus emerging during ferret transmission reduced polymerase and neuraminidase activity, constraining mammalian adaptation.

Virus

Host

Location

Supporting text

Airborne transmission in ferrets is accompanied by the mutations in PB1, NP and NA genes that reduce viral polymerase and neuraminidase activity. Therefore, while A(H7N9) virus can infect mammals, further adaptation appears to incur a fitness cost.

Genes or proteins: PB1; NP; NA
Mechanism types: polymerase_activity; pathogenicity; mammalian_adaptation

Citation context

References

61 references

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Evidence overview

Evidence 4

Types 4

Virus 1

Host 2

Evidence types

Cross Species Transmission 1 Genomic Evolution 1 Host Range Experiment 1 Molecular Adaptation 1

Linked entities

Viruses

Hosts

Locations

Publication metadata

Journal: Nature communications
Volume / Issue / Pages: 6 / - / 6553
ISSN: 2041-1723
Journal country: England
DOI: 10.1038/ncomms7553