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

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 100005, China

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Corresponding author: E-mail address: hbzhang2006@gmail.com (Hongbing Zhang)

Present address: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.

摘要

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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.
- Avian influenza /
- H5N1 /
- Autophagy /
- mTOR /
- TSC2 /
- PTEN
Present address: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
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