Three amino acid changes in PB1-F2 of highly pathogenic H5N1 avian influenza virus affect pathogenicity in mallard ducks

被引：44

作者：

Marjuki, Henju ^{[1
]}

Scholtissek, Christoph ^{[1
]}

Franks, John ^{[1
]}

Negovetich, Nicholas J. ^{[1
]}

Aldridge, Jerry R. ^{[1
]}

Salomon, Rachelle ^{[1
]}

Finkelstein, David ^{[2
]}

Webster, Robert G. ^{[1
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Infect Dis, Div Virol, Memphis, TN 38105 USA

[2] St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA

来源：

ARCHIVES OF VIROLOGY | 2010年 / 155卷 / 06期

基金：

美国国家卫生研究院;

关键词：

A/Vietnam/1203/2004; PB1-F2; Mallard ducks; H5N1; Highly pathogenic influenza A virus; A VIRUS; HONG-KONG; RNA-POLYMERASE; HIGH VIRULENCE; PROTEIN; EXPRESSION; GENERATION; SUBUNIT; BINDING; MODEL;

D O I：

10.1007/s00705-010-0666-4

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Despite reports that the PB1-F2 protein contributes to influenza virus pathogenicity in the mouse model, little is known about its significance in avian hosts. In our previous study, the A/Vietnam/1203/04 (H5N1) wild-type virus (wtVN1203) was more lethal to mallard ducks than a reverse genetics (rg)-derived VN1203. In search of potential viral factors responsible for this discrepancy, we found that synonymous mutations (SMs) had been inadvertently introduced into three genes of the rgVN1203 (rgVN1203/SM-3). Of 11 SMs in the PB1 gene, three resided in the PB1-F2 open reading frame, caused amino acid (aa) substitutions in the PB1-F2 protein, and reduced virus lethality in mallard ducks. The wtVN1203 and recombinant viruses with repairs to these three aa's (rgVN1203/R-PB1-F2) or with repairs to all 11 SMs (rgVN1203/R-PB1) were significantly more pathogenic than rgVN1203/SM-3. In cultured cells, repairing three mutations in PB1-F2 increased viral polymerase activity and expression levels of viral RNA.

引用

页码：925 / 934

页数：10

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