Three amino acid changes in PB1-F2 of highly pathogenic H5N1 avian influenza virus affect pathogenicity in mallard ducks.
Three amino acid changes in PB1-F2 of highly pathogenic H5N1 avian influenza virus affect pathogenicity in mallard ducks.
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高度致病的H5N1禽流感病毒的PB1-F2中的三种氨基酸变化会影响野鸭的致病性。
DOI：
10.1007/s00705-010-0666-4
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发表时间：
2010-06
影响因子：
2.7
通讯作者：
Webster, Robert G.
中科院分区：
文献类型：
--
作者：
Marjuki, Henju;Scholtissek, Christoph;Franks, John;Negovetich, Nicholas J.;Aldridge, Jerry R.;Salomon, Rachelle;Finkelstein, David;Webster, Robert G.
尽管有报道称PB 1-F2蛋白在小鼠模型中有助于流感病毒的致病性，但对其在禽类宿主中的意义知之甚少。在我们之前的研究中，A/Vietnam/1203/04（H5 N1）野生型病毒（wtVN 1203）对野鸭的致死性高于反向遗传（rg）衍生的VN 1203。在寻找导致这种差异的潜在病毒因素时，我们发现同义突变（SM）被无意中引入了rgVN 1203的3个基因（rgVN 1203/SM-3）。在PB 1基因的11个SM中，有3个SM位于PB 1-F2开放阅读框中，引起PB 1-F2蛋白的氨基酸（aa）替换，并降低病毒在野鸭中的致死率。wtVN 1203和对这3个氨基酸进行修复的重组病毒（rgVN 1203/R-PB 1-F2）或对所有11个SM进行修复的重组病毒（rgVN 1203/R-PB 1）比rgVN 1203/SM-3的致病性显著更高。在培养的细胞中，修复PB 1-F2中的3个突变增加了病毒聚合酶活性和病毒RNA的表达水平。
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 3 genes of the rgVN1203 (rgVN1203/SM-3). Of 11 SMs in the PB1 gene, 3 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 3 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 3 mutations in PB1-F2 increased viral polymerase activity and expression levels of viral RNA.
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