Adaptive amino acid substitutions enhance the virulence of an H7N7 avian influenza virus isolated from wild waterfowl in mice
Adaptive amino acid substitutions enhance the virulence of an H7N7 avian influenza virus isolated from wild waterfowl in mice
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DOI：
10.1016/j.vetmic.2015.02.016
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发表时间：
2015-05-15
影响因子：
3.3
通讯作者：
Hua, Yuping
中科院分区：
文献类型：
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作者：
Chen, Qiang;Yu, Zhijun;Hua, Yuping
尽管 H7N7 AIV 主要在野生水禽中传播，但记录在案的人类感染 H7N7 病毒的病例表明它们可能构成大流行威胁。在这里，我们生成了野生水禽源 H7N7 病毒的小鼠适应性变体，以识别赋予哺乳动物毒力增强的适应性变化。与亲本病毒相比，适应变体的小鼠致死剂量（MLD50）降低了>5000倍。小鼠适应性变体病毒在体外和体内表现出增强的复制，并获得了在肺外组织中复制的能力。这些观察结果表明，增强的生长特性和改变的细胞向性可能会增加 H7N7 AIV 在小鼠中的毒力。对适应性变异病毒的基因组分析揭示了 PB2 (E627K)、PB1 (R118I)、PA (L550M)、HA (G214R) 和 NA (S372N) 蛋白的氨基酸变化。我们的结果表明，这些氨基酸取代共同增强了 H7N7 病毒在哺乳动物中复制并引起严重疾病的能力。 (C) 2015 Elsevier B.V. 保留所有权利。
Although H7N7 AIVs primarily circulate in wild waterfowl, documented cases of human infection with H7N7 viruses suggest they may pose a pandemic threat. Here, we generated mouse-adapted variants of a wild waterfowl-origin H7N7 virus to identify adaptive changes that confer enhanced virulence in mammals. The mouse lethal doses (MLD50) of the adapted variants were reduced >5000-fold compared to the parental virus. Mouse-adapted variants viruses displayed enhanced replication in vitro and in vivo, and acquired the ability to replicate in extrapulmonary tissues. These observations suggest that enhanced growth characteristics and modified cell tropism may increase the virulence of H7N7 AIVs in mice. Genomic analysis of the adapted variant viruses revealed amino acid changes in the PB2 (E627K), PB1 (R118I), PA (L550M), HA (G214R), and NA (S372N) proteins. Our results suggest that these amino acid substitutions collaboratively enhance the ability of H7N7 virus to replicate and cause severe disease in mammals. (C) 2015 Elsevier B.V. All rights reserved.