Two Genetically Similar H9N2 Influenza A Viruses Show Different Pathogenicity in Mice.
Two Genetically Similar H9N2 Influenza A Viruses Show Different Pathogenicity in Mice.
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两种基因相似的 H9N2 甲型流感病毒在小鼠中表现出不同的致病性
DOI：
10.3389/fmicb.2016.01737
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发表时间：
2016
影响因子：
5.2
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Liu Q;Liu Y;Yang J;Huang X;Han K;Zhao D;Bi K;Li Y
H9 N2禽流感病毒已多次感染人类和其他哺乳动物，这突出了确定这种病毒对哺乳动物的致病性和相应机制的必要性。在本研究中，我们发现了两种具有相似遗传背景但在小鼠中具有不同致病性的H9 N2病毒。A/duck/Nanjing/06/2003（NJ 06）病毒对小鼠具有高致病性，其小鼠半数致死量（MLD 50）为102.83，而A/duck/Nanjing/01/1999（NJ 01）病毒对小鼠具有低致病性，其MLD 50>106.81 EID 50。进一步的研究表明，在体内和体外，NJ 06病毒生长更快，滴度明显高于NJ 01。此外，与NJ 01相比，NJ 06病毒诱导更严重的肺损伤，以及肺中更高水平的炎性细胞浸润和细胞因子应答。然而，只有12个不同的氨基酸残基，在两种病毒之间发现（HA-K157 E、NA-A9 T、NA-R435 K、PB 2-T149 P、PB 2-K627 E、PB 1-R187 K、PA-L548 M、PA-M550 L、NP-G127 E、NP-P277 H、NP-D340 N、NS 1-D171 N），除NA-R435 K外，其余残基均位于病毒蛋白相互作用或病毒与宿主因子相互作用的已知功能区。总之，我们的研究结果表明，多个氨基酸差异可能是NJ 06病毒对小鼠具有较高致病性的原因，导致致死性感染、增强的病毒复制、严重的肺部病变以及肺部过度的炎性细胞浸润和细胞因子反应。这些观察结果将有助于更好地了解未来可能对人类健康构成威胁的H9 N2病毒的致病潜力和相应的分子基础。
H9N2 Avian influenza virus has repeatedly infected humans and other mammals, which highlights the need to determine the pathogenicity and the corresponding mechanism of this virus for mammals. In this study, we found two H9N2 viruses with similar genetic background but with different pathogenicity in mice. The A/duck/Nanjing/06/2003 (NJ06) virus was highly pathogenic for mice, with a 50% mouse lethal dose (MLD50) of 102.83 50% egg infectious dose (EID50), whereas the A/duck/Nanjing/01/1999 (NJ01) virus was low pathogenic for mice, with a MLD50 of >106.81 EID50. Further studies showed that the NJ06 virus grew faster and reached significantly higher titers than NJ01 in vivo and in vitro. Moreover, the NJ06 virus induced more severe lung lesions, and higher levels of inflammatory cellular infiltration and cytokine response in lungs than NJ01 did. However, only 12 different amino acid residues (HA-K157E, NA-A9T, NA-R435K, PB2-T149P, PB2-K627E, PB1-R187K, PA-L548M, PA-M550L, NP-G127E, NP-P277H, NP-D340N, NS1-D171N) were found between the two viruses, and all these residues except for NA-R435K were located in the known functional regions involved in interaction of viral proteins or between the virus and host factors. Summary, our results suggest that multiple amino acid differences may be responsible for the higher pathogenicity of the NJ06 virus for mice, resulting in lethal infection, enhanced viral replication, severe lung lesions, and excessive inflammatory cellular infiltration and cytokine response in lungs. These observations will be helpful for better understanding the pathogenic potential and the corresponding molecular basis of H9N2 viruses that might pose threats to human health in the future.