title: Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck.
abstract: 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.
authors: 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.
authors: Hassan
authors: 0000000338076409
authors: H
authors: Zaraket
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Tatiana
authors: T
authors: Baranovich
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Bryan S
authors: BS
authors: Kaplan
authors: Department of Computation Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Robert
authors: R
authors: Carter
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Min-Suk
authors: MS
authors: Song
authors: 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.
authors: James C
authors: JC
authors: Paulson
authors: Department of Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Jerold E
authors: JE
authors: Rehg
authors: School of Public Health, The University of Texas Health Science Center at Houston, 1200 Pressler Street, Houston Texas 77030 USA.
authors: Justin
authors: 0000000175724300
authors: J
authors: Bahl
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Jeri C
authors: JC
authors: Crumpton
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Jon
authors: J
authors: Seiler
authors: Department of Computation Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Michael
authors: M
authors: Edmonson
authors: Department of Computation Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Gang
authors: 0000000216785864
authors: G
authors: Wu
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Erik
authors: E
authors: Karlsson
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Thomas
authors: T
authors: Fabrizio
authors: Joint Influenza Research Center (Shantou University Medical College &Hong Kong University), Shantou University Medical College, Shantou, Guangdong 515031, PR China.
authors: Huachen
authors: H
authors: Zhu
authors: Joint Influenza Research Center (Shantou University Medical College &Hong Kong University), Shantou University Medical College, Shantou, Guangdong 515031, PR China.
authors: Yi
authors: Y
authors: Guan
authors: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
authors: Matloob
authors: M
authors: Husain
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Stacey
authors: S
authors: Schultz-Cherry
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Scott
authors: S
authors: Krauss
authors: 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.
authors: Ryan
authors: R
authors: McBride
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Robert G
authors: RG
authors: Webster
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Elena A
authors: EA
authors: Govorkova
authors: Department of Computation Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678, USA.
authors: Jinghui
authors: J
authors: Zhang
authors: 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.
authors: Charles J
authors: CJ
authors: Russell
authors: 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.
authors: Richard J
authors: RJ
authors: Webby
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D058345:Asymptomatic Infections; D002645:Chickens; D002522:Chlorocebus aethiops; D004285:Dogs; D005289:Ferrets; D014644:Genetic Variation; D057809:HEK293 Cells; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics* / Q000472:pathogenicity; D005585:Influenza in Birds / Q000635:transmission / Q000821:virology*; D007251:Influenza, Human; D061985:Madin Darby Canine Kidney Cells; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000635:transmission / Q000821:virology*; D012367:RNA, Viral / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014709:Vero Cells; D014758:Viral Core Proteins / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
chemical_list: C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1; C487630:NA protein, influenza A virus; D009439:Neuraminidase