Abstract
Previous studies demonstrate that human enterovirus 71 (EV71), a primary causative agent for hand, foot, and mouth disease, activates caspase-3 through the non-structural viral 3C protein to induce host cell apoptosis; however, until now it was unclear how 3C activates caspase-3 and how caspase-3 activation affects viral production. Our results demonstrate that 3C binds caspase-8 and caspase-9 but does not directly bind caspase-3 to activate them, and that the proteolytic activity of 3C is required by the activation of caspase-8, caspase-9, and caspase-3. Inhibition of caspase-3 activity attenuates apoptosis in 3C-transfected cells. Furthermore, caspase-3 inhibitor protects host cells from the cytopathic effect of EV71 infection and prevents cell cycle arrest, which is known to be favored for EV71 viral replication. Inhibition of caspase-3 activity decreases EV71 viral protein expression and viral production, but has no effect on viral entry, replication, even polyprotein translation. Therefore, caspase-3 is exploited functionally by EV71 to facilitate its production, which suggests a novel therapeutic approach for the treatment and prevention of hand, foot, and mouth disease.
References
Feb 1, 1975·Journal of Virology·K V Holmes
Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·S HendersonA Rickinson
Nov 14, 1997·Trends in Biochemical Sciences·P VillaW C Earnshaw
Oct 31, 1997·Oncogene·L RaoE White
Dec 9, 1997·Cell·G S Salvesen, V M Dixit
Jul 17, 1998·Seminars in Cell & Developmental Biology·J M Hardwick
Oct 26, 2000·Nature·M O Hengartner
Mar 12, 2002·Virology·Mei-Ling LiShin-Ru Shih
Jan 23, 2003·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Tzou-Yien LinLuan-Yin Chang
May 30, 2003·The EMBO Journal·Walter J WurzerStephan Ludwig
Jul 16, 2004·Journal of Virology·Ya-Fang WangChun-Keung Yu
Mar 16, 2005·Journal of Neurovirology·Shih-Cheng ChangShin-Ru Shih
Jan 11, 2007·Apoptosis : an International Journal on Programmed Cell Death·Ulrike MartinAndreas Henke
Nov 23, 2007·Acta Pharmacologica Sinica·Jing-hua YuTakashi Ikejima
Jun 4, 2010·Journal of Virology·Xiaobo LeiJianwei Wang
Oct 22, 2010·The Lancet Infectious Diseases·Tom SolomonMong How Ooi
Mar 15, 2011·Journal of Molecular Biology·Sheng CuiQi Jin
Oct 8, 2011·PloS One·Michelle Y LiuJianguo Wu
Mar 10, 2012·Cell Death & Disease·A Richard, D Tulasne
Apr 6, 2012·PloS One·Xiaomei WangWenyan Zhang
Nov 24, 2012·Journal of Virology·Xiaobo LeiJianwei Wang
Nov 30, 2012·BMC Infectious Diseases·Weifeng ShiJinbo Liu
Mar 22, 2013·The Journal of General Virology·Jia-Rong LuSzu-Hao Kung
Dec 25, 2013·PLoS Neglected Tropical Diseases·Mei ZengQibin Leng
Feb 7, 2015·Cell Cycle·Jinghua YuXiao-Fang Yu
Jun 20, 2015·Cell Death and Differentiation·A R Burr, J D Molkentin
Sep 12, 2015·Drug Discovery Today·Qiaofeng WuXin Wang
Sep 16, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Liyan WangYonghong Liu
Oct 1, 2015·PloS One·Juanjuan GuiChangzheng Dong
Feb 11, 2016·Scientific Reports·Zhaolong LiXiao-Fang Yu
Apr 12, 2016·Frontiers in Microbiology·Jie LiYan He
Nov 15, 2016·Acta Pharmacologica Sinica·Ting ZhongJing-Hua Yu
Nov 17, 2016·Journal of Virology·Jing LiJuan Tan
Nov 20, 2016·The FEBS Journal·Brian D Larsen, Claus S Sørensen
Feb 22, 2017·Frontiers in Cellular and Infection Microbiology·Bingqing LiHong Meng
Feb 24, 2017·Frontiers in Cellular and Infection Microbiology·Zeng-Yan WangXiao-Fang Yu
Apr 30, 2017·The Journal of Biological Chemistry·Chunyang WangZheng Xing
May 26, 2017·Virology·Zhe ZhangWei Chen
Citations
Sep 13, 2019·Virologica Sinica·Bangtao ChenYihong Peng
Sep 10, 2019·PloS One·Mei-Ling LiGary Brewer
Sep 2, 2020·The Journal of Microbiology·Wenbo HuoShucheng Hua
Nov 22, 2018·Frontiers in Cellular and Infection Microbiology·Caiyun HuoYanxin Hu
Oct 23, 2018·Phytotherapy Research : PTR·Xiangling MengJinghua Yu
Mar 3, 2020·Frontiers in Microbiology·Shuxia ZhangJinghua Yu
Sep 19, 2020·Scientific Reports·Jhao-Yin Lin, Hsing-I Huang
Jun 26, 2020·Frontiers in Microbiology·Yalan LaiXiaoyue Chen
Mar 12, 2021·Journal of Cell Science·Jiamin YiHaixue Zheng