Highly pathogenic avian influenza A H5N1 and pandemic H1N1 virus infections have different phenotypes in Toll-like receptor 3 knockout mice
Highly pathogenic avian influenza A H5N1 and pandemic H1N1 virus infections have different phenotypes in Toll-like receptor 3 knockout mice
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DOI：
10.1099/vir.0.066258-0
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发表时间：
2014-09-01
影响因子：
3.8
通讯作者：
Peiris, J. S. Malik
中科院分区：
文献类型：
--
作者：
Leung, Y. H. Connie;Nicholls, John M.;Peiris, J. S. Malik
Toll样受体（TLR）在病毒感染的先天免疫中起重要作用。我们研究了TLR 3在H5 N1和大流行性H1N1（pH 1 N1）流感病毒感染小鼠的发病机制中的作用。用流感A/HK/486/97（H5 N1）或A/HK/415742/09（pH 1 N1）病毒感染野生型小鼠和TLR 3缺陷型小鼠。作为比较，骨髓分化因子88（MyD 88）基因缺陷的小鼠也感染了病毒，因为MyD 88通过与TLR 3不同的TLR途径发出信号。监测存活率和体重减轻14天，并研究肺病理学、肺免疫细胞谱、病毒载量和细胞因子反应。H5 N1感染的TLR 3（-/-）小鼠比H5 N1感染的WT小鼠具有更好的存活率，这通过体重明显更快地恢复、肺中更低的病毒滴度和肺中更少的病理变化来证明。然而，在TLR 3（-/-）小鼠的pH 1 N1感染后没有观察到这种改善的存活率。相比之下，MyD 88（-/-）小鼠在感染H5 N1病毒后肺中的病毒滴度增加，白细胞浸润减少，并且在pH 1 N1感染后存活率较差。结论：TLR 3参与了H5 N1感染的致病机制，而不是pH 1 N1感染的致病机制，这表明两种病毒的致病机制不同，TLR 3在两种病毒致病机制中的作用也不同。
Toll-like receptors (TLRs) play an important role in innate immunity to virus infections. We investigated the role of TLR3 in the pathogenesis of H5N1 and pandemic H1N1 (pH1N1) influenza virus infections in mice. Wild-type mice and those defective in TLR3 were infected with influenza A/HK/486/97 (H5N1) or A/HK/415742/09 (pH1N1) virus. For comparison, mice defective in the gene for myeloid differential factor 88 (MyD88) were also infected with the viruses, because MyD88 signals through a TLR pathway different from TLR3. Survival and body weight loss were monitored for 14 days, and lung pathology, the lung immune-cell profile, viral load and cytokine responses were studied. H5N1-infected TLR3(-/-) mice had better survival than H5N1-infected WT mice, evident by significantly faster regain of body weight, lower viral titre in the lung and fewer pathological changes in the lung. However, this improved survival was not seen upon pH1N1 infection of TLR3(-/-) mice. In contrast, MyD88(-/-) mice had an increased viral titre and decreased leukocyte infiltration in the lungs after infection with H5N1 virus and poorer survival after pH1N1 infection. In conclusion, TLR3 worsens the pathogenesis of H5N1 infection but not of pH1N1 infection, highlighting the differences in the pathogenesis of these two viruses and the different roles of TLR3 in their pathogenesis.