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禽流感病毒 H5N1 通过抑制 mTOR 信号通路诱导自噬介导的细胞死亡。

Avian influenza A virus H5N1 causes autophagy-mediated cell death through suppression of mTOR signaling.

机构信息

Department of Physiology and Pathophysiology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing.

出版信息

J Genet Genomics. 2011 Nov 20;38(11):533-7. doi: 10.1016/j.jgg.2011.10.002. Epub 2011 Oct 24.

Abstract

Of the few avian influenza viruses that have crossed the species barrier to infect humans, the highly pathogenic influenza A (H5N1) strain has claimed the lives of more than half of the infected patients. With largely unknown mechanism of lung injury by H5N1 infection, acute respiratory distress syndrome (ARDS) is the major cause of death among the victims. Here we present the fact that H5N1 caused autophagic cell death through suppression of mTOR signaling. Inhibition of autophagy, either by depletion of autophagy gene Beclin1 or by autophagy inhibitor 3-methyladenine (3-MA), significantly reduced H5N1 mediated cell death. We suggest that autophagic cell death may contribute to the development of ARDS in H5N1 influenza patients and inhibition of autophagy could therefore become a novel strategy for the treatment of H5N1 infection.

摘要

在少数能够跨越物种屏障感染人类的禽流感病毒中,高致病性流感病毒 A(H5N1)已导致半数以上感染者死亡。由于对 H5N1 感染导致肺损伤的机制了解甚少,急性呼吸窘迫综合征(ARDS)是此类患者死亡的主要原因。本研究证实,H5N1 通过抑制 mTOR 信号通路引发自噬细胞死亡。通过敲除自噬基因 Beclin1 或自噬抑制剂 3-甲基腺嘌呤(3-MA)抑制自噬,均可显著减少 H5N1 介导的细胞死亡。我们认为,自噬细胞死亡可能导致 H5N1 流感患者发生 ARDS,因此抑制自噬可能成为治疗 H5N1 感染的新策略。

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