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Journal of Virology, January 2008, p. 220-228, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.00978-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Naturally Occurring Deletion in Its NS Gene Contributes to the Attenuation of an H5N1 Swine Influenza Virus in Chickens{triangledown}

Qiyun Zhu,1 Huanliang Yang,1 Weiye Chen,1 Wenyan Cao,1 Gongxun Zhong,1 Peirong Jiao,1 Guohua Deng,1 Kangzhen Yu,1 Chinglai Yang,2 Zhigao Bu,1 Yoshihiro Kawaoka,3 and Hualan Chen1*

Animal Influenza Laboratory of the Ministry of Agriculture and National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 427 Maduan Street, Harbin 150001, People's Republic of China,1 Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322,2 Institute of Medical Sciences, University of Tokyo, Tokyo 108-8639, Japan3

Received 7 May 2007/ Accepted 3 October 2007

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.

* Corresponding author. Mailing address: Harbin Veterinary Research Institute, 427 Maduan Street, Harbin 150001, People's Republic of China. Phone: (86)-451-82761925. Fax: (86)-451-82733132. E-mail: hlchen1{at}yahoo.com

{triangledown} Published ahead of print on 17 October 2007.

Journal of Virology, January 2008, p. 220-228, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.00978-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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