title: Attenuation of the virulence of a recombinant influenza virus expressing the naturally truncated NS gene from an H3N8 equine influenza virus in mice.
abstract: Equine influenza virus (EIV) causes a highly contagious disease in horses and other equids. Recently, we isolated an H3N8 EIV (A/equine/Kyonggi/SA1/2011) from a domestic horse in South Korea that exhibited symptoms of respiratory disease, and found that the EIV strain contained a naturally mutated NS gene segment encoding a truncated NS1 protein. In order to determine whether there was an association between the NS gene truncation and viral virulence, a reverse genetics system was applied to generate various NS gene recombinant viruses using the backbone of the H1N1 A/Puerto Rico/8/1934 (PR/8) virus. In a mouse model, the recombinant PR/8 virus containing the mutated NS gene of the Korean H3N8 EIV strain showed a dramatically reduced virulence: it induced no weight loss, no clinical signs and no histopathological lesions. However, the mice infected with the recombinant viruses with NS genes of PR/8 and H3N8 A/equine/2/Miami/1963 showed severe clinical signs including significant weight loss and 100% mortality. In addition, the levels of the pro-inflammatory cytokines; IL-6, CCL5, and IFN-γ, in the lungs of mice infected with the recombinant viruses expressing a full-length NS1 were significantly higher than those of mice infected with the virus with the NS gene from the Korean H3N8 EIV strain. In this study, our results suggest that the C-terminal moiety of NS1 contains a number of virulence determinants and might be a suitable target for the development of a vaccine candidate against equine influenza.
authors.affiliation: College of Pharmacy, Korea University, Sejong, Republic of Korea.
authors.forename: Woonsung
authors.initials: W
authors.lastname: Na
authors.affiliation: Korea Zoonosis Research Institute, Chonbuk National University, Iksan, Republic of Korea.
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Lyoo
authors.affiliation: Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Sun-Woo
authors.initials: SW
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Korea University, Sejong, Republic of Korea.
authors.forename: Minjoo
authors.initials: M
authors.lastname: Yeom
authors.affiliation: Research Unit, Green Cross Veterinary Products, Yong-in, Republic of Korea.
authors.forename: Bokyu
authors.initials: B
authors.lastname: Kang
authors.affiliation: Research Unit, Green Cross Veterinary Products, Yong-in, Republic of Korea.
authors.forename: Hyoungjoon
authors.initials: H
authors.lastname: Moon
authors.affiliation: Korea Zoonosis Research Institute, Chonbuk National University, Iksan, Republic of Korea.
authors.forename: Hye Kwon
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Korea Zoonosis Research Institute, Chonbuk National University, Iksan, Republic of Korea.
authors.forename: Dae Gwin
authors.initials: DG
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Korea University, Sejong, Republic of Korea. kfrancis@korea.ac.kr.
authors.forename: Jeong-Ki
authors.initials: JK
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Korea University, Sejong, Republic of Korea. sds1@korea.ac.kr.
authors.forename: Daesub
authors.initials: D
authors.lastname: Song
mesh_terms: D000072283:A549 Cells; D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D004285:Dogs; D057809:HEK293 Cells; D006734:Horse Diseases / Q000276:immunology / Q000821:virology; D006736:Horses; D006801:Humans; D053123:Influenza A Virus, H3N8 Subtype / Q000235:genetics / Q000472:pathogenicity; D008168:Lung / Q000473:pathology / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D011995:Recombination, Genetic / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000276:immunology; D010948:Viral Plaque Assay
chemical_list: D016207:Cytokines; C108309:NS protein, influenza virus; D017361:Viral Nonstructural Proteins