Characteristics of two highly pathogenic avian influenza H5N8 viruses with different pathogenicity in mice.
Characteristics of two highly pathogenic avian influenza H5N8 viruses with different pathogenicity in mice.
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两种对小鼠致病力不同的高致病性禽流感H5N8病毒的特征。
DOI：
10.1007/s00705-016-3043-0
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Liu Xiufan
中科院分区：
文献类型：
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作者：
Wang Xiao;Meng Feifei;Wang D;an;Liu Xing;Chen Sujuan;Qin Tao;Peng Daxin;Liu Xiufan
新型甲型H5 N8流感病毒不仅对家禽业，而且对公共卫生构成潜在威胁。在其他H5亚型禽流感病毒中，也发现了许多与哺乳动物宿主致病性相关的分子标记。然而，H5 N8禽流感病毒对哺乳动物的致病性仍不清楚。因此，选择一对遗传背景相似但对哺乳动物毒力不同的分离株是研究禽流感病毒致病机制的前提。本研究以两株具有相似遗传背景（H5进化枝2.3.4.4）和致病性分子标记的禽源H5 N8分离株A/goose/Eastern China/CZ/2013（CZ 13）和A/duck/ Eastern China /JY/2014（JY 14）为研究对象，对其生物学特性和致病性进行了研究。使用α-2，3-唾液酸酶处理的鹅红细胞进行的血凝试验表明，两种病毒均表现出双受体结合偏好。体外病毒生长动力学研究表明，两种病毒在CEF细胞中均能高滴度复制（约108.0TCID50/mL）。而在MDCK细胞中，CZ 13的增殖效率很高（107.0TCID50/mL），而JY 14的最高滴度低于104.0TCID50/mL。动物研究表明，尽管这两种病毒在鸡中的毒力很强，但它们在小鼠中的毒力却有显著差异。CZ 13为高致病性（MLD 50 = 101.6EID 50），JY 14为低致病性（MLD 50> 106.5EID 50）。因此，这对病毒可用于寻找未知的毒力分子标记，并在小鼠中研究特定的致病机制。
Novel reassortant influenza A (H5N8) viruses are becoming a potential threat not only to the poultry industry but also to public health. Many molecular markers for pathogenicity in mammalian hosts have been identified in other H5 subtype avian influenza viruses (AIVs). However, the pathogenicity of H5N8 AIVs to mammals remains unclear. It is believed that selection of a pair of isolates with a similar genetic background but with different virulence to mammals is a prerequisite for studying the pathogenic mechanism of AIVs. Two avian-origin H5N8 isolates, A/goose/Eastern China/CZ/2013 (CZ13) and A/duck/ Eastern China /JY/2014 (JY14), which shared a similar genetic background (H5 clade 2.3.4.4) and amino acid substitutions that were shown previously to be molecular markers of pathogenicity, were used to determine their biological characteristics and pathogenicity. Hemagglutination assays using α-2,3-sialidase-treated goose red blood cells demonstrated that both viruses exhibited a dual-receptor-binding preference. Viral growth kineticsin vitroindicated that both viruses replicated to high titers in CEF cells (about 108.0TCID50/mL). In MDCK cells, however, CZ13 replicated efficiently (107.0TCID50/mL), while JY14 grew to peak titers below 104.0TCID50/mL. Animal studies indicated that although both viruses were highly virulent in chickens, they exhibited significantly different virulence in mice. CZ13 was highly pathogenic (MLD50= 101.6EID50), whereas JY14 had low virulence (MLD50> 106.5EID50). Therefore, this pair of viruses can be used to search for unknown molecular markers of virulence and to investigate specific pathogenic mechanisms in mice.