Although stress has been known to increase the susceptibility of pathogen infection,the underlying mechanism remains elusive.In this study,we reported that restraint stress dramatically enhanced the morbidity and mort...Although stress has been known to increase the susceptibility of pathogen infection,the underlying mechanism remains elusive.In this study,we reported that restraint stress dramatically enhanced the morbidity and mortality of mice infected with the influenza virus(H1N1)and obviously aggravated lung inflammation.Corticosterone(CORT),a main type of glucocorticoids in rodents,was secreted in the plasma of stressed mice.We further found that this stress hormone significantly boosted virus replication by restricting mitochondrial antiviral signaling(MAVS)protein-transduced IFN-βproduction without affecting its mRNA level,while the deficiency of MAVS abrogated stress/CORT-induced viral susceptibility in mice.Mechanistically,the effect of CORT was mediated by proteasome-dependent degradation of MAVS,thereby resulting in the impediment of MAVS-transduced IFN-βgeneration in vivo and in vitro.Furthermore,RNA-seq assay results indicated the involvement of Mitofusin 2(Mfn2)in this process.Gain-and loss-offunction experiments indicated that Mfn2 interacted with MAVS and recruited E3 ligase SYVN1 to promote the polyubiquitination of MAVS.Co-immunoprecipitation experiments clarified an interaction between any two regions of Mfn2(HR1),MAVS(C-terminal/TM)and SYVN1(TM).Collectively,our findings define the Mfn2-SYVN1 axis as a new signaling cascade for proteasome-dependent degradation of MAVS and a‘fine tuning’of antiviral innate immunity in response to influenza infection under stress.展开更多
Dear Editor,COVID-19 cases showed a significant decrease in the number of peripheral CD4^(+) and CD8^(+)T cells accompanied by overactivation of cells.1 HHV8-derived viral macrophage inflammatory protein vMIP-Ⅱ is th...Dear Editor,COVID-19 cases showed a significant decrease in the number of peripheral CD4^(+) and CD8^(+)T cells accompanied by overactivation of cells.1 HHV8-derived viral macrophage inflammatory protein vMIP-Ⅱ is the only broad-spectrum chemokine receptor inhibitor that binds to three subtribes of chemokine receptors,which can significantly increase the specific cell immune response in infected organisms and have an effect of reducing plasma viral load on the viremia period.24 Here we report the effect of vMIP-Ⅱ in COVID-19.展开更多
基金supported,in part,by Natural Science Foundation of China(grant numbers 81622050,81573675,U1801284,81673709,81873209)National Key Research and Development Program of China(grant number 2017YFC1700404)+4 种基金the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(grant number 2017BT01Y036)and GDUPS(2019)the Guangdong Science and Technology Foundation for Distinguished Young Scholars(grant number 2017A030306004)the Youth Top-notch Talent Support Program of Guangdong Province(2016TQ03R586)the Program of Hong Kong Scholar(XJ2016017)the Science and Technology Program of Guangzhou(grant number 201903010062).
文摘Although stress has been known to increase the susceptibility of pathogen infection,the underlying mechanism remains elusive.In this study,we reported that restraint stress dramatically enhanced the morbidity and mortality of mice infected with the influenza virus(H1N1)and obviously aggravated lung inflammation.Corticosterone(CORT),a main type of glucocorticoids in rodents,was secreted in the plasma of stressed mice.We further found that this stress hormone significantly boosted virus replication by restricting mitochondrial antiviral signaling(MAVS)protein-transduced IFN-βproduction without affecting its mRNA level,while the deficiency of MAVS abrogated stress/CORT-induced viral susceptibility in mice.Mechanistically,the effect of CORT was mediated by proteasome-dependent degradation of MAVS,thereby resulting in the impediment of MAVS-transduced IFN-βgeneration in vivo and in vitro.Furthermore,RNA-seq assay results indicated the involvement of Mitofusin 2(Mfn2)in this process.Gain-and loss-offunction experiments indicated that Mfn2 interacted with MAVS and recruited E3 ligase SYVN1 to promote the polyubiquitination of MAVS.Co-immunoprecipitation experiments clarified an interaction between any two regions of Mfn2(HR1),MAVS(C-terminal/TM)and SYVN1(TM).Collectively,our findings define the Mfn2-SYVN1 axis as a new signaling cascade for proteasome-dependent degradation of MAVS and a‘fine tuning’of antiviral innate immunity in response to influenza infection under stress.
基金This work was supported by National Natural Science Foundation of China(NSFC Nos.82073747,82074133)Su Yuan biotechnology co.Ltd.
文摘Dear Editor,COVID-19 cases showed a significant decrease in the number of peripheral CD4^(+) and CD8^(+)T cells accompanied by overactivation of cells.1 HHV8-derived viral macrophage inflammatory protein vMIP-Ⅱ is the only broad-spectrum chemokine receptor inhibitor that binds to three subtribes of chemokine receptors,which can significantly increase the specific cell immune response in infected organisms and have an effect of reducing plasma viral load on the viremia period.24 Here we report the effect of vMIP-Ⅱ in COVID-19.
