Objective:It is well known that stress plays a critical role in immune response and susceptibility to diseases.Among many stressors,restraint stress has been shown to suppress immune function and increase susceptibili...Objective:It is well known that stress plays a critical role in immune response and susceptibility to diseases.Among many stressors,restraint stress has been shown to suppress immune function and increase susceptibility to infections.In this study,we employed a restraint-mouse model to investigate the effect and preliminary mechanism of ShiQi herbal tea(SQHT),a traditional Chinese medicine,on H1N1 virus infection.Methods:Mice were exposed to restraint stress and infected with H1N1 influenza virus by intranasal inoculation.SQHT(936 and 1872 mg/kg/d)was orally administrated to mice for 7 days from the first day of restraint stress.The survival rate of mice in each group was monitored daily for 21 days.Histopathological changes,inflammatory cells infiltration,and virus titer in lungs were examined.For the study of mechanisms,we investigated whether SQHT could promote interferon-β(IFN-β)generation and interferon stimulated genes(ISG)expression.Results:Our results suggested that SQHT(936 mg/kg/d)significantly reduced H1N1-induced mortality,the level of complement C5a and lung tissue inflammation,and viral replication in restraint-stressed mice.Further results revealed that in restraint-stressed mice model,SQHT(936 mg/kg/d)administration markedly improved IFN-βgeneration,and increased MX1 and IFITM3 gene expression.Conclusion:Our study demonstrates that SQHT reduces restraint stress-induced susceptibility to H1N1 infection via improving IFN-βantiviral pathway,which provides a certain basis for the clinical use of SQHT to treat H1N1 infection.展开更多
Herpes simplex virus type 1(HSV-1),a neurotropic herpes virus,is able to establish a lifelong latent infection in the human host.Following primary replication in mucosal epithelial cells,the virus can enter sensory ne...Herpes simplex virus type 1(HSV-1),a neurotropic herpes virus,is able to establish a lifelong latent infection in the human host.Following primary replication in mucosal epithelial cells,the virus can enter sensory neurons innervating peripheral tissues via nerve termini.The viral genome is then transported to the nucleus where it can be maintained without producing infectious progeny,and thus latency is established in the cell.Yin-Yang balance is an essential concept in traditional Chinese medicine(TCM)theory.Yin represents stable and inhibitory factors,and Yang represents the active and aggressive factors.When the organism is exposed to stress,especially psychological stress caused by emotional stimulation,the Yin-Yang balance is disturbed and the virus can re-engage in productive replication,resulting in recurrent diseases.Therefore,a better understanding of the stress-induced susceptibility to HSV-1 primary infection and reactivation is needed and will provide helpful insights into the effective control and treatment of HSV-1.Here we reviewed the recent advances in the studies of HSV-1 susceptibility,latency and reactivation.We included mechanisms involved in primary infection and the regulation of latency and described how stress-induced changes increase the susceptibility to primary and recurrent infections.展开更多
Herpes simplex virus type 1(HSV-1)is a ubiquitous and widespread human pathogen,which gives rise to a range of diseases,including cold sores,corneal blindness,and encephalitis.Currently,the use of nucleoside analogs,s...Herpes simplex virus type 1(HSV-1)is a ubiquitous and widespread human pathogen,which gives rise to a range of diseases,including cold sores,corneal blindness,and encephalitis.Currently,the use of nucleoside analogs,such as acyclovir and penciclovir,in treating HSV-1 infection often presents limitation due to their side effects and low efficacy for drug-resistance strains.Therefore,new anti-herpetic drugs and strategies should be urgently developed.Here,we reported that baicalein,a naturally derived compound widely used in Asian countries,strongly inhibited HSV-1 replication in several models.Baicalein was effective against the replication of both HSV-1/F and HSV-1/Blue(an acyclovir-resistant strain)in vitro.In the ocular inoculation mice model,baicalein markedly reduced in vivo HSV-1/F replication,receded inflammatory storm and attenuated histological changes in the cornea.Consistently,baicalein was found to reduce the mortality of mice,viral loads both in nose and trigeminal ganglia in HSV-1 intranasal infection model.Moreover,an ex vivo HSV-1-EGFP infection model established in isolated murine epidermal sheets confirmed that baicalein suppressed HSV-1 replication.Further investigations unraveled that dual mechanisms,inactivating viral particles and inhibiting IκB kinase beta(IKK-β)phosphorylation,were involved in the anti-HSV-1 effect of baicalein.Collectively,our findings identified baicalein as a promising therapy candidate against the infection of HSV-1,especially acyclovir-resistant strain.展开更多
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
基金This work was financially supported,in part,by Science and Technology Project of Zhongshan(2013A3FC0253)Scientific Research Team Training Project in University of Electronic Science and Technology of China,Zhongshan Institute(No.412YT02)Natural Science Foundation of Guangdong Province-the Ph.D.Startup and Vertical Collaboration Project(2018030310186).
文摘Objective:It is well known that stress plays a critical role in immune response and susceptibility to diseases.Among many stressors,restraint stress has been shown to suppress immune function and increase susceptibility to infections.In this study,we employed a restraint-mouse model to investigate the effect and preliminary mechanism of ShiQi herbal tea(SQHT),a traditional Chinese medicine,on H1N1 virus infection.Methods:Mice were exposed to restraint stress and infected with H1N1 influenza virus by intranasal inoculation.SQHT(936 and 1872 mg/kg/d)was orally administrated to mice for 7 days from the first day of restraint stress.The survival rate of mice in each group was monitored daily for 21 days.Histopathological changes,inflammatory cells infiltration,and virus titer in lungs were examined.For the study of mechanisms,we investigated whether SQHT could promote interferon-β(IFN-β)generation and interferon stimulated genes(ISG)expression.Results:Our results suggested that SQHT(936 mg/kg/d)significantly reduced H1N1-induced mortality,the level of complement C5a and lung tissue inflammation,and viral replication in restraint-stressed mice.Further results revealed that in restraint-stressed mice model,SQHT(936 mg/kg/d)administration markedly improved IFN-βgeneration,and increased MX1 and IFITM3 gene expression.Conclusion:Our study demonstrates that SQHT reduces restraint stress-induced susceptibility to H1N1 infection via improving IFN-βantiviral pathway,which provides a certain basis for the clinical use of SQHT to treat H1N1 infection.
基金supported,in part,by the National Key Research and Development Program of China,China(grant number2017YFC1700404)Natural Science Foundation of China,China(grant numbers 81622050,81573675,81673709,81560661 and81873209)+3 种基金the Young Top-notch Talent Support Program of Guangdong Province,China(grant numbers 2014TQ01R229 and2016TQ03R586)Guangdong Province Ocean and Fisheries Bureau-Key Technology Research and Development Program,China(grant number A201701A02)Guangdong Science and Technology Foundation for Distinguished Young Scholars,China(grant number 2017A030306004)the Science and Technology Program of Guangzhou,China(grant numbers 201604046016 and201610010182).
文摘Herpes simplex virus type 1(HSV-1),a neurotropic herpes virus,is able to establish a lifelong latent infection in the human host.Following primary replication in mucosal epithelial cells,the virus can enter sensory neurons innervating peripheral tissues via nerve termini.The viral genome is then transported to the nucleus where it can be maintained without producing infectious progeny,and thus latency is established in the cell.Yin-Yang balance is an essential concept in traditional Chinese medicine(TCM)theory.Yin represents stable and inhibitory factors,and Yang represents the active and aggressive factors.When the organism is exposed to stress,especially psychological stress caused by emotional stimulation,the Yin-Yang balance is disturbed and the virus can re-engage in productive replication,resulting in recurrent diseases.Therefore,a better understanding of the stress-induced susceptibility to HSV-1 primary infection and reactivation is needed and will provide helpful insights into the effective control and treatment of HSV-1.Here we reviewed the recent advances in the studies of HSV-1 susceptibility,latency and reactivation.We included mechanisms involved in primary infection and the regulation of latency and described how stress-induced changes increase the susceptibility to primary and recurrent infections.
基金partly supported by National Natural Science Foundation of China(Grant Nos.U1801284,81573675,81622050,81873209 and 81673709)National Key Research and Development Program of China(Grant No.2017YFC1700404)+5 种基金the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(Grant No.2017BT01Y036,China)GDUPS(2019,China)the Guangdong Science and Technology Foundation(Grant No.2017A030306004)the Program of Hong Kong Scholar(XJ2016017,China)Science and Technology Program of Guangzhou(Grant No.201903010062,China)the Youth Top-notch Talent Support Program of Guangdong Province(Grant No.2016TQ03R586,China)
文摘Herpes simplex virus type 1(HSV-1)is a ubiquitous and widespread human pathogen,which gives rise to a range of diseases,including cold sores,corneal blindness,and encephalitis.Currently,the use of nucleoside analogs,such as acyclovir and penciclovir,in treating HSV-1 infection often presents limitation due to their side effects and low efficacy for drug-resistance strains.Therefore,new anti-herpetic drugs and strategies should be urgently developed.Here,we reported that baicalein,a naturally derived compound widely used in Asian countries,strongly inhibited HSV-1 replication in several models.Baicalein was effective against the replication of both HSV-1/F and HSV-1/Blue(an acyclovir-resistant strain)in vitro.In the ocular inoculation mice model,baicalein markedly reduced in vivo HSV-1/F replication,receded inflammatory storm and attenuated histological changes in the cornea.Consistently,baicalein was found to reduce the mortality of mice,viral loads both in nose and trigeminal ganglia in HSV-1 intranasal infection model.Moreover,an ex vivo HSV-1-EGFP infection model established in isolated murine epidermal sheets confirmed that baicalein suppressed HSV-1 replication.Further investigations unraveled that dual mechanisms,inactivating viral particles and inhibiting IκB kinase beta(IKK-β)phosphorylation,were involved in the anti-HSV-1 effect of baicalein.Collectively,our findings identified baicalein as a promising therapy candidate against the infection of HSV-1,especially acyclovir-resistant strain.
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.