title: A naturally occurring deletion in its NS gene contributes to the attenuation of an H5N1 swine influenza virus in chickens.
abstract: In 2001 and 2003, we isolated two H5N1 viruses, A/swine/Fujian/1/01 (SW/FJ/01) and A/swine/Fujian/1/03 (SW/FJ/03), from pigs in Fujian Province, southern China. Genetically, these two viruses are similar, although the NS gene of the SW/FJ/03 virus has a 15-nucleotide deletion at coding positions 612 to 626. The SW/FJ/01 virus is highly lethal for chickens, whereas the SW/FJ/03 virus is nonpathogenic for chickens when administrated intravenously or intranasally. To understand the molecular basis for the difference in virulence, we used reverse genetics to create a series of single-gene recombinants of both viruses. We found that a recombinant virus containing the mutated NS gene from the SW/FJ/03 virus in the SW/FJ/01 virus background was completely attenuated in chickens. We also found that viruses expressing the mutant NS1 protein of SW/FJ/03 did not antagonize the induction of interferon (IFN) protein. Conversely, only the recombinant virus containing the wild-type SW/FJ/01 NS gene in the SW/FJ/03 background was lethal in chickens and antagonized IFN protein levels. Further, we proved that the NS1 genes of the two viruses differ in their stabilities in the host cells and in their abilities to interact with the chicken cleavage and polyadenylation specificity factor. These results indicate that the deletion of amino acids 191 to 195 of the NS1 protein is critical for the attenuation of the SW/FJ/03 virus in chickens and that this deletion affects the ability of the virus to antagonize IFN induction in host cells.
authors.affiliation: Harbin Veterinary Research Institute, 427 Maduan Street, Harbin 150001, People's Republic of China.
authors.forename: Qiyun
authors.initials: Q
authors.lastname: Zhu
authors.forename: Huanliang
authors.initials: H
authors.lastname: Yang
authors.forename: Weiye
authors.initials: W
authors.lastname: Chen
authors.forename: Wenyan
authors.initials: W
authors.lastname: Cao
authors.forename: Gongxun
authors.initials: G
authors.lastname: Zhong
authors.forename: Peirong
authors.initials: P
authors.lastname: Jiao
authors.forename: Guohua
authors.initials: G
authors.lastname: Deng
authors.forename: Kangzhen
authors.initials: K
authors.lastname: Yu
authors.forename: Chinglai
authors.initials: C
authors.lastname: Yang
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Bu
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Hualan
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000821:virology; D002642:Chick Embryo; D002645:Chickens; D005260:Female; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D005585:Influenza in Birds / Q000821:virology*; D007372:Interferons / Q000037:antagonists & inhibitors / Q000276:immunology; D007668:Kidney / Q000821:virology; D007928:Lethal Dose 50; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D017384:Sequence Deletion; D013154:Spleen / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000276:immunology; D014774:Virulence / Q000235:genetics
chemical_list: C108309:NS protein, influenza virus; D017361:Viral Nonstructural Proteins; D007372:Interferons