title: C-terminal elongation of NS1 of H9N2 influenza virus induces a high level of inflammatory cytokines and increases transmission.
abstract: H9N2 avian influenza viruses are enzootic around the world and can infect many different avian and mammalian hosts, including humans. Unlike the H9N2 viruses, which mainly originated in other countries and possess a non-structural protein 1 (NS1) of 230 aa, 98 % of the H9N2 viruses isolated in China lack the 13 aa at the C terminus of NS1 (217 aa in total). The biological significance of NS1 elongation remains elusive. To examine the effect of NS1 C-terminal elongation in the influenza virus, we used reverse genetics to generate a wt avian influenza H9N2 virus containing a 217 aa NS1 (H9N2NS1217) and two mutant viruses with elongated NS1s of 230 and 237 aa (H9N2NS1230 and H9N2NS1237). C-terminal elongation of NS1 did not have a significant impact on virus replication in Madin-Darby canine kidney cells or DF-1 cells. The three variants exhibited similar replicability in mice; however, the H9N2NS1230 and H9N2NS1237 variants exhibited an upregulation in the level of inflammatory cytokines. In addition, both the H9N2NS1230 and H9N2NS1237 viruses increased replication and induced a high level of inflammatory cytokines and transmission in chickens, compared with the wt virus. These findings suggest that the NS1 extension conferred a gain of fitness to some extent.
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Weili
authors.initials: W
authors.lastname: Kong
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Lirong
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: He
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Sizhe
authors.initials: S
authors.lastname: Wu
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Sun
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Pu
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D002681:China; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D054884:Host-Pathogen Interactions; D053127:Influenza A Virus, H9N2 Subtype / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D005585:Influenza in Birds / Q000473:pathology / Q000635:transmission / Q000821:virology; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000635:transmission / Q000821:virology; D059386:Reverse Genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
chemical_list: D016207:Cytokines; C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins