tetano
Editor, Senior Moderator
The Journal of Infectious Diseases 2010;202:000?000
? 2010 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2010/20209-00XX$15.00
DOI: 10.1086/656536
MAJOR ARTICLE
Effect on Virulence and Pathogenicity of H5N1 Influenza A Virus through Truncations of NS1 eIF4GI Binding Domain
Hongbo Zhou,a
Jiping Zhu,a
Jiagang Tu,
Wei Zou,
Yong Hu,
Zhengjun Yu,
Wensi Yin,
Yongtao Li,
Anding Zhang,
Yurong Wu,
Ziniu Yu,
Huanchun Chen, and
Meilin Jin
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China
To study the effect of NS1 eIF4GI binding domain on virulence and pathogenicity of H5N1 influenza A virus, 5 recombinant H5N1 viruses encoding eIF4GI binding domain?truncated NS1 proteins and parental NS1 (NS1‐wt) were generated by an 8‐plasmid?based reverse genetics system. The results indicated that the recombinants with the addition of 5‐amino acid and the deletion position of 85?89 in NS1‐wt were attenuated in replication in vitro and in vivo, compared with the recombinant wild‐type virus rNS1‐wt, whereas the deletion position 85?94 or the entire eIF4GI binding domain in NS1‐wt displayed a significantly attenuated phenotype in chicken and mice. We also showed that the eIF4GI binding domain?truncated mutants were impaired in their ability to inhibit interferon production in vitro, and they did not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in Madin ‐Darby Canine Kidney cells, or in vivo in chickens and in a mouse model. Therefore, these attenuated NS1‐truncated viruses may have a great potential as live attenuated vaccine candidates against H5N1 influenza A virus.
http://www.journals.uchicago.edu/doi/abs/10.1086/656536
? 2010 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2010/20209-00XX$15.00
DOI: 10.1086/656536
MAJOR ARTICLE
Effect on Virulence and Pathogenicity of H5N1 Influenza A Virus through Truncations of NS1 eIF4GI Binding Domain
Hongbo Zhou,a
Jiping Zhu,a
Jiagang Tu,
Wei Zou,
Yong Hu,
Zhengjun Yu,
Wensi Yin,
Yongtao Li,
Anding Zhang,
Yurong Wu,
Ziniu Yu,
Huanchun Chen, and
Meilin Jin
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China
To study the effect of NS1 eIF4GI binding domain on virulence and pathogenicity of H5N1 influenza A virus, 5 recombinant H5N1 viruses encoding eIF4GI binding domain?truncated NS1 proteins and parental NS1 (NS1‐wt) were generated by an 8‐plasmid?based reverse genetics system. The results indicated that the recombinants with the addition of 5‐amino acid and the deletion position of 85?89 in NS1‐wt were attenuated in replication in vitro and in vivo, compared with the recombinant wild‐type virus rNS1‐wt, whereas the deletion position 85?94 or the entire eIF4GI binding domain in NS1‐wt displayed a significantly attenuated phenotype in chicken and mice. We also showed that the eIF4GI binding domain?truncated mutants were impaired in their ability to inhibit interferon production in vitro, and they did not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in Madin ‐Darby Canine Kidney cells, or in vivo in chickens and in a mouse model. Therefore, these attenuated NS1‐truncated viruses may have a great potential as live attenuated vaccine candidates against H5N1 influenza A virus.
http://www.journals.uchicago.edu/doi/abs/10.1086/656536