Influenza is a persistent threat to human health and there is a continuing requirement for updating antiinfluenza strategies. Initiated by observations of different endoplasmic reticulum(ER) responses of host to seaso...Influenza is a persistent threat to human health and there is a continuing requirement for updating antiinfluenza strategies. Initiated by observations of different endoplasmic reticulum(ER) responses of host to seasonal H1N1 and highly pathogenic avian influenza(HPAI) A H5N1 infections, we identified an alternative antiviral role of tauroursodeoxycholic acid(TUDCA), a clinically available ER stress inhibitor, both in vitro and in vivo. Rather than modulating ER stress in host cells, TUDCA abolished the proton conductivity of viral M2 by disrupting its oligomeric states, which induces inefficient viral infection. We also showed that M2 penetrated cells, whose intracellular uptake depended on its proton channel activity,an effect observed in both TUDCA and M2 inhibitor amantadine. The identification and application of TUDCA as an inhibitor of M2 proton channel will expand our understanding of IAV biology and complement current anti-IAV arsenals.展开更多
Following the published article[1].the authors noticed an error duplication of image of DAPI in Fig.2c"AF"and"No pretreated and without TUDCA".The correct DAPI image was in the merged image of"...Following the published article[1].the authors noticed an error duplication of image of DAPI in Fig.2c"AF"and"No pretreated and without TUDCA".The correct DAPI image was in the merged image of"No pretreated and without TUDCA"of the published article.Therefore,the corrected Fig.2c should be as follows:The online version of the original artice can be found at https://doi.org/10.101/j.scib.2018.08.0131.展开更多
基金supported by the National Natural Science Foundation of China (81788101, 81573587 and 81490531)the Ministry of Science and Technology of China (2015CB5534/6)+3 种基金111 project (B08007)the Peking Union Medical College Youth FundFundamental Research Funds for Central Universities (3332013132)the CAMS Innovation Fund for Medical Sciences (2017-I2M-1-009)
文摘Influenza is a persistent threat to human health and there is a continuing requirement for updating antiinfluenza strategies. Initiated by observations of different endoplasmic reticulum(ER) responses of host to seasonal H1N1 and highly pathogenic avian influenza(HPAI) A H5N1 infections, we identified an alternative antiviral role of tauroursodeoxycholic acid(TUDCA), a clinically available ER stress inhibitor, both in vitro and in vivo. Rather than modulating ER stress in host cells, TUDCA abolished the proton conductivity of viral M2 by disrupting its oligomeric states, which induces inefficient viral infection. We also showed that M2 penetrated cells, whose intracellular uptake depended on its proton channel activity,an effect observed in both TUDCA and M2 inhibitor amantadine. The identification and application of TUDCA as an inhibitor of M2 proton channel will expand our understanding of IAV biology and complement current anti-IAV arsenals.
文摘Following the published article[1].the authors noticed an error duplication of image of DAPI in Fig.2c"AF"and"No pretreated and without TUDCA".The correct DAPI image was in the merged image of"No pretreated and without TUDCA"of the published article.Therefore,the corrected Fig.2c should be as follows:The online version of the original artice can be found at https://doi.org/10.101/j.scib.2018.08.0131.
