Glycine at Position 622 in PB1 Contributes to the Virulence of H5N1 Avian Influenza Virus in Mice

被引：75

作者：

Feng, Xiaoxiao ^{[1
]}

Wang, Zeng ^{[1
]}

Shi, Jianzhong ^{[1
]}

Deng, Guohua ^{[1
]}

Kong, Huihui ^{[1
]}

Tao, Shiyu ^{[1
]}

Li, Changyao ^{[1
]}

Liu, Liling ^{[1
]}

Guan, Yuntao ^{[1
]}

Chen, Hualan ^{[1
]}

机构：

[1] Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Vet Biotechnol, Harbin, Peoples R China

来源：

JOURNAL OF VIROLOGY | 2016年 / 90卷 / 04期

基金：

中国国家自然科学基金;

关键词：

A VIRUS; RNA-POLYMERASE; RESPIRATORY DROPLET; MOLECULAR-BASIS; HYBRID VIRUSES; VIRAL-RNA; PROTEIN; SUBUNIT; PA; TRANSMISSION;

D O I：

10.1128/JVI.02387-15

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

We isolated two H5N1 viruses, A/duck/Hunan/S4020/2008 (DK/08) and A/chicken/Guangxi/S2039/2009 (CK/09), from live-bird markets during routine surveillance and found that these two viruses are genetically similar but differ in their replication and virulence in mice. The CK/09 virus is lethal for mice with a 50% mouse lethal dose (MLD50) of 1.6 log(10) 50% egg infectious doses (EID50), whereas the DK/08 virus is nonpathogenic for mice with an MLD50 value of 6.2 log(10) EID50. We explored the genetic basis of the virulence difference of these two viruses by generating a series of reassortant viruses and mutants in the lethal virus CK/09 background and evaluating their virulence in mice. We found that the PB1 gene of the DK/08 virus dramatically attenuated the virulence of the CK/09 virus and that the amino acid at position 622 in PB1 made an important contribution. We further demonstrated that the mutation of glycine (G) to aspartic acid (D) at position 622 in PB1 partially impaired the binding of PB1 to viral RNA, thereby dramatically decreasing the polymerase activity and attenuating H5N1 virus virulence in mice. Our results identify a novel virulence-related marker of H5N1 influenza viruses and provide a new target for live attenuated vaccine development.

引用

页码：1872 / 1879

页数：8

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