H9 avian influenza reassortant with engineered polybasic cleavage site displays a highly pathogenic phenotype in chicken
H9 avian influenza reassortant with engineered polybasic cleavage site displays a highly pathogenic phenotype in chicken
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DOI：
10.1099/vir.0.031591-0
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发表时间：
2011-08-01
影响因子：
3.8
通讯作者：
Stech, Juergen
中科院分区：
文献类型：
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作者：
Gohrbandt, Sandra;Veits, Jutta;Stech, Juergen
在野外，高致病性禽流感病毒（HPAIV）来源于血凝素（HA）血清型H5和H7的低致病性毒株，其已经获得了多碱性HA切割位点。这一观察结果表明，H5和H7低致病性禽流感病毒（LPAIV）存在潜在的隐蔽毒力。在所有其他LPAIV中，H9N2毒株具有特别的相关性，因为它们已经在许多国家的几种鸟类中广泛传播，并已传播给人类。为了评估这些毒株转化为HPAIV的潜力，我们将一个多碱基切割位点引入到当代H9N2分离株的HA中。而工程化的多碱HA切割位点突变体仍然是一个低致病性的菌株，如其亲本病毒，一个replicant表达的修饰H9 HA与工程化的多碱切割位点和所有其他基因从H5N1 HPAIV成为高致病性鸡静脉内致病性指数为1.23。这些结果表明，H5或H7亚型以外的HPAIV只会出现在HA基因可以获得一个多碱基切割位点和其他病毒基因携带额外的毒力决定簇的条件下。
In the field, highly pathogenic avian influenza viruses (HPAIV) originate from low-pathogenic strains of the haemagglutinin (HA) serotypes H5 and H7 that have acquired a polybasic HA cleavage site. This observation suggests the presence of a cryptic virulence potential of H5 and H7 low-pathogenic avian influenza viruses (LPAIV). Among all other LPAIV, the H9N2 strains are of particular relevance as they have become widespread across many countries in several avian species and have been transmitted to humans. To assess the potential of these strains to transform into an HPAIV, we introduced a polybasic cleavage site into the HA of a contemporary H9N2 isolate. Whereas the engineered polybasic HA cleavage site mutant remained a low-pathogenic strain like its parent virus, a reassortant expressing the modified H9 HA with engineered polybasic cleavage site and all the other genes from an H5N1 HPAIV became highly pathogenic in chicken with an intravenous pathogenicity index of 1.23. These results suggest that an HPAIV with a subtype other than H5 or H7 would only emerge under conditions where the HA gene could acquire a polybasic cleavage site and the other viral genes carry additional virulence determinants.