title: Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus.
abstract: The endemicity of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Asia has led to the generation of reassortant H5 strains with novel gene constellations. A newly emerged HPAI A(H5N8) virus caused poultry outbreaks in the Republic of Korea in 2014. Because newly emerging high-pathogenicity H5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. Here, we characterized A/mallard duck/Korea/W452/2014 (MDk/W452(H5N8)), a representative virus, and evaluated its pathogenic and pandemic potential in various animal models. We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks. Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues. In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses. It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding. Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection. With their potential to become established in ducks, continued circulation of A(H5N8) viruses could alter the genetic evolution of pre-existing avian poultry strains. Overall, detailed virological investigation remains a necessity given the capacity of H5 viruses to evolve to cause human illness with few changes in the viral genome.
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Philippe Noriel Q
authors.initials: PN
authors.lastname: Pascua
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Hyeok-Il
authors.initials: HI
authors.lastname: Kwon
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Gyo-Jin
authors.initials: GJ
authors.lastname: Lim
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Eun-Ha
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology , Daejeon 305-806, Korea.
authors.forename: Sun-Woo
authors.initials: SW
authors.lastname: Yoon
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Se Mi
authors.initials: SM
authors.lastname: Kim
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Choi
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Young-Jae
authors.initials: YJ
authors.lastname: Si
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Ok-Jun
authors.initials: OJ
authors.lastname: Lee
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Woo-Sub
authors.initials: WS
authors.lastname: Shim
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Si-Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: In-Pil
authors.initials: IP
authors.lastname: Mo
authors.affiliation: College of Veterinary Medicine, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Yeonji
authors.initials: Y
authors.lastname: Bae
authors.affiliation: SKKU Advanced Institute of Technology and Department of Chemical Engineering, Sungkyunkwan University , Suwon 440-746, Korea.
authors.forename: Yong Taik
authors.initials: YT
authors.lastname: Lim
authors.affiliation: Department of Advanced Fermentation Fusion Science & Technology, Kookmin University , Seoul 136-702, Korea ; BioLeaders Corporation, Yongsandong, Yuseong-gu, Daejeon 305-500, Korea.
authors.forename: Moon Hee
authors.initials: MH
authors.lastname: Sung
authors.affiliation: College of Veterinary Medicine, Chungnam National University , Daejeon 305-764, Korea.
authors.forename: Chul-Joong
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital , Memphis, TN 38105-3678, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital , Memphis, TN 38105-3678, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Webster
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 361-763, Korea.
authors.forename: Young Ki
authors.initials: YK
authors.lastname: Choi
keywords: HPAI A(H5N8); avian influenza virus; genetic evolution; migratory waterfowl; reassortment