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PMID: 17942562 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A naturally occurring deletion in its NS gene contributes to the attenuation of an H5N1 swine influenza virus in chickens.

Journal of virology ·Vol. 82 ·No. 1 ·2008-01-00 ·Pages 220-8

Zhu Q, Yang H, Chen W, Cao W, Zhong G, Jiao P, Deng G, Yu K, Yang C, Bu Z, Kawaoka Y, Chen H

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.

MeSH Terms
Animals Brain/virology Chick Embryo Chickens Female Influenza A Virus, H5N1 Subtype/genetics,immunology,isolation & purification,pathogenicity Influenza A virus/genetics,immunology,isolation & purification,pathogenicity Influenza in Birds/virology Interferons/antagonists & inhibitors,immunology Kidney/virology Lethal Dose 50 Lung/virology Mice Mice, Inbred BALB C Sequence Deletion Spleen/virology Viral Nonstructural Proteins/genetics,immunology Virulence/genetics
Chemicals
NS protein, influenza virus Viral Nonstructural Proteins Interferons
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Zhu Qiyun
Harbin Veterinary Research Institute, 427 Maduan Street, Harbin 150001, People's Republic of China.
Yang Huanliang
Chen Weiye
Cao Wenyan
Zhong Gongxun
Jiao Peirong
Deng Guohua
Yu Kangzhen
Yang Chinglai
Bu Zhigao
Kawaoka Yoshihiro
Chen Hualan
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
1098-5514
DOI
10.1128/JVI.00978-07
Published
2008-01-00
Epub
2007-00-17
Pages
220-8
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC2224367
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.00978-07 PMC Full Text View journal details
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