The Lipid Mediator Protectin D1 Inhibits Influenza Virus Replication and Improves Severe Influenza
The Lipid Mediator Protectin D1 Inhibits Influenza Virus Replication and Improves Severe Influenza
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DOI：
10.1016/j.cell.2013.02.027
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发表时间：
2013-03-28
期刊：
影响因子：
64.5
通讯作者：
Imai, Yumiko
中科院分区：
文献类型：
--
作者：
Morita, Masayuki;Kuba, Keiji;Imai, Yumiko
甲型流感病毒是导致死亡的主要原因。考虑到未来致命性大流行的可能性，需要有效的药物来治疗严重的流感，如由H5 N1病毒引起的流感。使用介体脂质组学和生物活性脂质筛选，我们报告称，ω-3多不饱和脂肪酸（PUFA）衍生的脂质介体保护素D1（PD 1）通过RNA输出机制显着减弱流感病毒复制。在严重流感期间，PD 1的产生受到抑制，PD 1水平与H5 N1病毒的致病性呈负相关。PD 1的抑制在遗传上与12/15-脂氧合酶活性有关。重要的是，PD 1治疗改善了小鼠严重流感的存活率和病理学，即使在已知抗病毒药物无法保护小鼠免于死亡的情况下。这些结果鉴定了内源性脂质介质PD 1作为流感病毒复制的先天抑制因子，其保护免于致死性流感病毒感染。
Influenza A viruses are a major cause of mortality. Given the potential for future lethal pandemics, effective drugs are needed for the treatment of severe influenza such as that caused by H5N1 viruses. Using mediator lipidomics and bioactive lipid screen, we report that the omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator protectin D1 (PD1) markedly attenuated influenza virus replication via RNA export machinery. Production of PD1 was suppressed during severe influenza and PD1 levels inversely correlated with the pathogenicity of H5N1 viruses. Suppression of PD1 was genetically mapped to 12/15-lipoxygenase activity. Importantly, PD1 treatment improved the survival and pathology of severe influenza in mice, even under conditions where known antiviral drugs fail to protect from death. These results identify the endogenous lipid mediator PD1 as an innate suppressor of influenza virus replication that protects against lethal influenza virus infection.