title: Selective Bottlenecks Shape Evolutionary Pathways Taken during Mammalian Adaptation of a 1918-like Avian Influenza Virus.
abstract: Avian influenza virus reassortants resembling the 1918 human pandemic virus can become transmissible among mammals by acquiring mutations in hemagglutinin (HA) and polymerase. Using the ferret model, we trace the evolutionary pathway by which an avian-like virus evolves the capacity for mammalian replication and airborne transmission. During initial infection, within-host HA diversity increased drastically. Then, airborne transmission fixed two polymerase mutations that do not confer a detectable replication advantage. In later transmissions, selection fixed advantageous HA1 variants. Transmission initially involved a "loose" bottleneck, which became strongly selective after additional HA mutations emerged. The stringency and evolutionary forces governing between-host bottlenecks may therefore change throughout host adaptation. Mutations occurred in multiple combinations in transmitted viruses, suggesting that mammalian transmissibility can evolve through multiple genetic pathways despite phenotypic constraints. Our data provide a glimpse into avian influenza virus adaptation in mammals, with broad implications for surveillance on potentially zoonotic viruses.
authors: Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI 53706, USA; Wisconsin National Primate Research Center, Madison, WI 53715, USA.
authors: Louise H
authors: LH
authors: Moncla
authors: Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI 53706, USA.
authors: Gongxun
authors: G
authors: Zhong
authors: Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
authors: Chase W
authors: CW
authors: Nelson
authors: Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI 53706, USA; Wisconsin National Primate Research Center, Madison, WI 53715, USA.
authors: Jorge M
authors: JM
authors: Dinis
authors: Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI 53706, USA; Wisconsin National Primate Research Center, Madison, WI 53715, USA.
authors: James
authors: J
authors: Mutschler
authors: Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
authors: Austin L
authors: AL
authors: Hughes
authors: Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI 53706, USA; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors: Tokiko
authors: T
authors: Watanabe
authors: Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI 53706, USA; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Electronic address: kawaokay@vetmed.wisc.edu.
authors: Yoshihiro
authors: Y
authors: Kawaoka
authors: Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI 53706, USA; Wisconsin National Primate Research Center, Madison, WI 53715, USA. Electronic address: thomasf@primate.wisc.edu.
authors: Thomas C
authors: TC
authors: Friedrich
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D005075:Biological Evolution; D001717:Birds; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000502:physiology*; D005585:Influenza in Birds / Q000635:transmission / Q000821:virology*; D007251:Influenza, Human / Q000635:transmission / Q000821:virology*; D008322:Mammals / Q000821:virology*; D009976:Orthomyxoviridae Infections / Q000635:transmission / Q000821:virology*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus