title: The PDZ-binding motif of the avian NS1 protein affects transmission of the 2009 influenza A(H1N1) virus.
abstract: By nature of their segmented RNA genome, influenza A viruses (IAVs) have the potential to generate variants through a reassortment process. The influenza nonstructural (NS) gene is critical for a virus to counteract the antiviral responses of the host. Therefore, a newly acquired NS segment potentially determines the replication efficiency of the reassortant virus in a range of different hosts. In addition, the C-terminal PDZ-binding motif (PBM) has been suggested as a pathogenic determinant of IAVs. To gauge the pandemic potential from human and avian IAV reassortment, we assessed the replication properties of NS-reassorted viruses in cultured cells and in the lungs of mice and determined their transmissibility in guinea pigs. Compared with the recombinant A/Korea/01/2009 virus (rK09; 2009 pandemic H1N1 strain), the rK09/VN:NS virus, in which the NS gene was adopted from the A/Vietnam/1203/2004 virus (a human isolate of the highly pathogenic avian influenza H5N1 virus strains), exhibited attenuated virulence and reduced transmissibility. However, the rK09/VN:NS-PBM virus, harboring the PBM in the C-terminus of the NS1 protein, recovered the attenuated virulence of the rK09/VN:NS virus. In a guinea pig model, the rK09/VN:NS-PBM virus showed even greater transmission efficiency than the rK/09 virus. These results suggest that the PBM in the NS1 protein may determine viral persistence in the human and avian IAV interface.
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul 136-705, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, Republic of Korea.
authors.forename: Jin Il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul 136-705, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, Republic of Korea.
authors.forename: Min-Woong
authors.initials: MW
authors.lastname: Hwang
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul 136-705, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, Republic of Korea.
authors.forename: Ilseob
authors.initials: I
authors.lastname: Lee
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul 136-705, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, Republic of Korea.
authors.forename: Sehee
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul 136-705, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, Republic of Korea.
authors.forename: Sangmoo
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul 136-705, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, Republic of Korea.
authors.forename: Joon-Yong
authors.initials: JY
authors.lastname: Bae
authors.affiliation: Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, Republic of Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Heo
authors.affiliation: Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, Republic of Korea.
authors.forename: Donghwan
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, Republic of Korea.
authors.forename: Seok-Il
authors.initials: SI
authors.lastname: Jang
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul 136-705, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, Republic of Korea.
authors.forename: Mee Sook
authors.initials: MS
authors.lastname: Park
authors.affiliation: Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, Republic of Korea.
authors.forename: Hyung-Joo
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul 136-705, Republic of Korea.
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Song
authors.affiliation: Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul 136-705, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, Republic of Korea. Electronic address: manseong.park@gmail.com.
authors.forename: Man-Seong
authors.initials: MS
authors.lastname: Park
mesh_terms: D000818:Animals; D001717:Birds; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000635:transmission* / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D054731:PDZ Domains; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism*; D014775:Virus Activation / Q000502:physiology; D014779:Virus Replication / Q000502:physiology
chemical_list: C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins
keywords: Influenza A virus; Interferon; NS1 protein; PDZ-binding motif; Transmission