Inflammatory markers are elevated in people with the zoonotic disease Mpox(formerly known as monkeypox),but how the monkeypox virus(MPXV)drives these responses has remained largely undefined.A new study published in C...Inflammatory markers are elevated in people with the zoonotic disease Mpox(formerly known as monkeypox),but how the monkeypox virus(MPXV)drives these responses has remained largely undefined.A new study published in Cellular&Molecular Immunology[1]revealed that the cytosolic DNA sensor AIM2 triggers inflammasome responses and pyroptosis in MPXV-infected cells,leading to apoptotic and necroptotic cell death in uninfected bystander macrophages.展开更多
Active host-pathogen interactions take place during infection of human immunodeficiency virus type 1 (HIV-1). Outcomes of these interactions determine the efficiency of viral infection and subsequent disease progressi...Active host-pathogen interactions take place during infection of human immunodeficiency virus type 1 (HIV-1). Outcomes of these interactions determine the efficiency of viral infection and subsequent disease progression. HIV- infected cells respond to viral invasion with various defensive strategies such as innate, cellular and humoral immune antiviral mechanisms. On the other hand, the virus has also developed various offensive tactics to suppress these host cellular responses. Among many of the viral offensive strategies, HIV-1 viral auxiliary proteins (Tat, Rev, Nef, Vif, Vpr and Vpu) play important roles in the host-pathogen interaction and thus have significant impacts on the outcome of HIV infection. One of the best examples is the interaction of Vif with a host cytidine deaminase APOBEC3G. Although specific roles of other auxiliary proteins are not as well described as Vif-APOBEC3G interaction, it is the goal of this brief review to summarize some of the preliminary findings with the hope to stimulate further discussion and investiga- tion in this exhilarating area of research.展开更多
Human knowledge of viruses has experienced explosive growth in the 21st century.This leap forward is reflected not only in the deepening of basic research on viruses but also in addressing public health challenges pos...Human knowledge of viruses has experienced explosive growth in the 21st century.This leap forward is reflected not only in the deepening of basic research on viruses but also in addressing public health challenges posed by viral diseases.Key advancements include the rapid identification of emerging viruses and variants,the revelation of diverse viromes and evolutionary patterns,the elucidation of viral pathogenesis-and antiviral targets,as well as development of novel vaccines and antiviral drugs through far more advanced techniques and pipelines(Holmes et al.,2024).Altogether,these breakthroughs are reshaping our understanding of viruses and our strategies to combat viral infections at an unprecedented pace.展开更多
Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is pre...Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) response.These chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors.Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C.The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection.When the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic damage.The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell migration.Some chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome.The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.展开更多
Eastern equine encephalitis virus(EEEV)is a lethal Alphavirus transmitted by Culiseta melanura mosquitoes that primarily cycles between birds.Although rare,infections in humans and horses are associated with high mort...Eastern equine encephalitis virus(EEEV)is a lethal Alphavirus transmitted by Culiseta melanura mosquitoes that primarily cycles between birds.Although rare,infections in humans and horses are associated with high mortality rates and severe neurological effects.Climate change appears to be increasing the spread of this virus.This study aims to provide a comprehensive analysis of EEEV,including its transmission dynamics,pathogenesis,induced host immune response,and long-term impacts on survivors.It also highlights the virus's unique immune evasion strategies that complicate disease management and contribute to severe clinical outcomes,such as encephalitis with fever,convulsions,and coma.Survivors often face chronic cognitive,motor,and psychosocial impairments.Despite these significant public health risks,gaps remain in understanding the molecular mechanisms underlying immune evasion and the long-term neurological sequelae in survivors.By collating current knowledge,this review underscores the urgent need for the development of targeted vaccines and therapeutic interventions to mitigate the growing threat of EEEV,particularly in the context of climate change-driven geographical expansion.展开更多
Plant viruses are a group of intracellular pathogens that persistently threaten global food security.Significant advances in plant virology have been achieved by Chinese scientists over the last 20 years,including bas...Plant viruses are a group of intracellular pathogens that persistently threaten global food security.Significant advances in plant virology have been achieved by Chinese scientists over the last 20 years,including basic research and technologies for preventing and controlling plant viral diseases.Here,we review these milestones and advances,including the identification of new crop-infecting viruses,dissection of pathogenic mechanisms of multiple viruses,examination of multilayered interactions among viruses,their host plants,and virus-transmitting arthropod vectors,and in-depth interrogation of plantencoded resistance and susceptibility determinants.Notably,various plant virus-based vectors have also been successfully developed for gene function studies and target gene expression in plants.We also recommend future plant virology studies in China.展开更多
The Coronavirus disease 2019(COVID-19)has posed a serious threat to global health and the world economy.Antiviral therapies targeting coronavirus are urgently required.The Cepharanthine(CEP)is a traditional Chinese he...The Coronavirus disease 2019(COVID-19)has posed a serious threat to global health and the world economy.Antiviral therapies targeting coronavirus are urgently required.The Cepharanthine(CEP)is a traditional Chinese herbal extract.Our previous research revealed that CEP has a very potent anti-coronavirus effect,but its mechanism of action was not fully understood.To investigate the effect of novel coronavirus on protein glycosylation in infected cells and to further investigate the mechanism of action of CEP against coronavirus,a cellular model using coronavirus GX_P2V infection of Vero E6 cells was established.The effect of coronavirus GX_P2V on host cell protein glycosylation was investigated by N-glycoproteomic analysis,and the antagonistic effect of CEP on the abnormal protein glycosylation caused by coronavirus was analyzed.The results showed that GX_P2V could cause abnormal changes in protein glycosylation levels in host cells,while CEP could partially antagonize the abnormal protein glycosylation caused by GX_P2V.In addition,we also found that CEP could regulate the glycosylation level of coronavirus S protein.In conclusion,this article provides important ideas about the infection mechanism of novel coronaviruses,providing evidence for CEP as a promising therapeutic option for coronavirus infection.展开更多
A robust innate and adaptive immune response is essential to viral clearance.Hepatitis C virus(HCV)infection typically leads to alteration of the innate and adaptive immune response,which is caused by interaction of H...A robust innate and adaptive immune response is essential to viral clearance.Hepatitis C virus(HCV)infection typically leads to alteration of the innate and adaptive immune response,which is caused by interaction of HCV core protein with various host factors.It is important to investigate the alterations to the immune response during the transition from acute HCV to chronic HCV infection to develop better therapeutic methods for HCV infection.In this work,to determine whether HCV viral persistence occurs via tumor necrosis apoptosis-inducing ligand(TRAIL)-mediated apoptosis,we stimulated peripheral blood mononuclear cells(PBMCs)with recombinant HCV core protein within 12 h to measure the relative expression of death receptors 4 and 5(DR4 and DR5)in PBMCs.We show that recombinant HCV core protein causes increased DR4 and DR5 expression in PBMCs.We also show that TRAIL interacts with DR4 and DR5 after cleavage of membrane-bound TRAIL yielding soluble TRAIL.Our results show that HCV core protein increases PBMC susceptibility to apoptosis and may cause increased TRAIL pathway activity within 12 h of infection.In addition,we observed that increased death receptor expression may contribute to HCV pathogenesis,as typically observed in chronically HCV-infected individuals.展开更多
Investigation of the bi-directional relationship between natural killer(NK)cells and plasmacytoid dendritic cells(pDCs)is critical in understanding antiviral immunity.In the present study,we determined whether the tum...Investigation of the bi-directional relationship between natural killer(NK)cells and plasmacytoid dendritic cells(pDCs)is critical in understanding antiviral immunity.In the present study,we determined whether the tumor necrosis factor apoptosis-inducing ligand(TRAIL)pathway was responsible for increased apoptosis of pDCs in hepatitis C virus(HCV)infection.We stimulated peripheral blood mononuclear cells(PBMCs)with recombinant HCV core protein within 12 hours to measure the relative expression of tumor necrosis factor apoptosis-inducing receptor 1(TRAIL-R1)and TRAIL-R2 in pDCs using flow cytometry and image cytometry.We also measured the relative expression of TRAIL in NK cells after stimulation with recombinant HCV core protein using flow cytometry and image cytometry.Using flow cytometry,our results show that within 12 hours of stimulation,HCV core protein increases TRAIL-R1 on pDCs by 0.01%,CD56 expression by 0.66%,and TRAIL expression by 0.66%,in NK cells as compared to unstimulated PBMCs.ELISA and fluorescence spectroscopy results showed that HCV core protein decreases Bcl-2 expression in PBMCs and in pDCs by 36%and 3%,respectively.Our results suggest that HCV core protein increases NK cell deletion of pDCs,independent of the Bcl-2 pathway,contributing to HCV viral escape from immune responses,which may result in chronic HCV infection.展开更多
基金HB is supported by an Australian Government Research Training Program(RTP)Stipend ScholarshipAP is supported by a Medical Research Future Fund(MRFF)Early to Mid-Career Researchers grant(2041535)+3 种基金an ANU Hansen Scandinavian Friendship GrantSMM is supported by the National Health and Medical Research Council(NHMRC)of Australia(under Investigator Grant 2026910)the Australian Government Australia-India Strategic Research Fund and Collaborative Research Project(AIRXV000005)a CSL Centenary Fellowship。
文摘Inflammatory markers are elevated in people with the zoonotic disease Mpox(formerly known as monkeypox),but how the monkeypox virus(MPXV)drives these responses has remained largely undefined.A new study published in Cellular&Molecular Immunology[1]revealed that the cytosolic DNA sensor AIM2 triggers inflammasome responses and pyroptosis in MPXV-infected cells,leading to apoptotic and necroptotic cell death in uninfected bystander macrophages.
文摘Active host-pathogen interactions take place during infection of human immunodeficiency virus type 1 (HIV-1). Outcomes of these interactions determine the efficiency of viral infection and subsequent disease progression. HIV- infected cells respond to viral invasion with various defensive strategies such as innate, cellular and humoral immune antiviral mechanisms. On the other hand, the virus has also developed various offensive tactics to suppress these host cellular responses. Among many of the viral offensive strategies, HIV-1 viral auxiliary proteins (Tat, Rev, Nef, Vif, Vpr and Vpu) play important roles in the host-pathogen interaction and thus have significant impacts on the outcome of HIV infection. One of the best examples is the interaction of Vif with a host cytidine deaminase APOBEC3G. Although specific roles of other auxiliary proteins are not as well described as Vif-APOBEC3G interaction, it is the goal of this brief review to summarize some of the preliminary findings with the hope to stimulate further discussion and investiga- tion in this exhilarating area of research.
文摘Human knowledge of viruses has experienced explosive growth in the 21st century.This leap forward is reflected not only in the deepening of basic research on viruses but also in addressing public health challenges posed by viral diseases.Key advancements include the rapid identification of emerging viruses and variants,the revelation of diverse viromes and evolutionary patterns,the elucidation of viral pathogenesis-and antiviral targets,as well as development of novel vaccines and antiviral drugs through far more advanced techniques and pipelines(Holmes et al.,2024).Altogether,these breakthroughs are reshaping our understanding of viruses and our strategies to combat viral infections at an unprecedented pace.
基金Supported by Grants from "Fiscam" J.C.C.M (Ayuda paraproyectos de investigación en saludPI-2007/32)+7 种基金"AsociaciónCastellana de Aparato Digestivo" (Beca ACADACAD/06)"Fundación de Investigación Médica Mutua Madrilea"(Beca Ayudas a la Investigación FMMM2548/2008),Spainsupported by a research grantfrom "Fiscam" J.C.C.M ("Perfeccionamiento y movilidad deinvestigadores" MOV-2007_JI/18), Spainsupported by a research grant from "Instituto de SaludCarlos Ⅲ" (Contrato de apoyo a la investigación en el SNS"CA07/00157),Spain
文摘Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) response.These chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors.Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C.The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection.When the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic damage.The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell migration.Some chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome.The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.
文摘Eastern equine encephalitis virus(EEEV)is a lethal Alphavirus transmitted by Culiseta melanura mosquitoes that primarily cycles between birds.Although rare,infections in humans and horses are associated with high mortality rates and severe neurological effects.Climate change appears to be increasing the spread of this virus.This study aims to provide a comprehensive analysis of EEEV,including its transmission dynamics,pathogenesis,induced host immune response,and long-term impacts on survivors.It also highlights the virus's unique immune evasion strategies that complicate disease management and contribute to severe clinical outcomes,such as encephalitis with fever,convulsions,and coma.Survivors often face chronic cognitive,motor,and psychosocial impairments.Despite these significant public health risks,gaps remain in understanding the molecular mechanisms underlying immune evasion and the long-term neurological sequelae in survivors.By collating current knowledge,this review underscores the urgent need for the development of targeted vaccines and therapeutic interventions to mitigate the growing threat of EEEV,particularly in the context of climate change-driven geographical expansion.
基金the National Natural Science Foundation of China for financial support(31530062 and 32025031)。
文摘Plant viruses are a group of intracellular pathogens that persistently threaten global food security.Significant advances in plant virology have been achieved by Chinese scientists over the last 20 years,including basic research and technologies for preventing and controlling plant viral diseases.Here,we review these milestones and advances,including the identification of new crop-infecting viruses,dissection of pathogenic mechanisms of multiple viruses,examination of multilayered interactions among viruses,their host plants,and virus-transmitting arthropod vectors,and in-depth interrogation of plantencoded resistance and susceptibility determinants.Notably,various plant virus-based vectors have also been successfully developed for gene function studies and target gene expression in plants.We also recommend future plant virology studies in China.
基金the National Key Research and Development Program of China(2018YFA0903000)the National Natural Science Foundation of China(81672001)+2 种基金China MoST Emergency Project on COVID-19(2020YFC0840800)Guangdong Basic and Applied Basic Research Foundation(2021A1515110619)the Fundamental Research Funds for the Central Universities(KG16052901).
文摘The Coronavirus disease 2019(COVID-19)has posed a serious threat to global health and the world economy.Antiviral therapies targeting coronavirus are urgently required.The Cepharanthine(CEP)is a traditional Chinese herbal extract.Our previous research revealed that CEP has a very potent anti-coronavirus effect,but its mechanism of action was not fully understood.To investigate the effect of novel coronavirus on protein glycosylation in infected cells and to further investigate the mechanism of action of CEP against coronavirus,a cellular model using coronavirus GX_P2V infection of Vero E6 cells was established.The effect of coronavirus GX_P2V on host cell protein glycosylation was investigated by N-glycoproteomic analysis,and the antagonistic effect of CEP on the abnormal protein glycosylation caused by coronavirus was analyzed.The results showed that GX_P2V could cause abnormal changes in protein glycosylation levels in host cells,while CEP could partially antagonize the abnormal protein glycosylation caused by GX_P2V.In addition,we also found that CEP could regulate the glycosylation level of coronavirus S protein.In conclusion,this article provides important ideas about the infection mechanism of novel coronaviruses,providing evidence for CEP as a promising therapeutic option for coronavirus infection.
文摘A robust innate and adaptive immune response is essential to viral clearance.Hepatitis C virus(HCV)infection typically leads to alteration of the innate and adaptive immune response,which is caused by interaction of HCV core protein with various host factors.It is important to investigate the alterations to the immune response during the transition from acute HCV to chronic HCV infection to develop better therapeutic methods for HCV infection.In this work,to determine whether HCV viral persistence occurs via tumor necrosis apoptosis-inducing ligand(TRAIL)-mediated apoptosis,we stimulated peripheral blood mononuclear cells(PBMCs)with recombinant HCV core protein within 12 h to measure the relative expression of death receptors 4 and 5(DR4 and DR5)in PBMCs.We show that recombinant HCV core protein causes increased DR4 and DR5 expression in PBMCs.We also show that TRAIL interacts with DR4 and DR5 after cleavage of membrane-bound TRAIL yielding soluble TRAIL.Our results show that HCV core protein increases PBMC susceptibility to apoptosis and may cause increased TRAIL pathway activity within 12 h of infection.In addition,we observed that increased death receptor expression may contribute to HCV pathogenesis,as typically observed in chronically HCV-infected individuals.
文摘Investigation of the bi-directional relationship between natural killer(NK)cells and plasmacytoid dendritic cells(pDCs)is critical in understanding antiviral immunity.In the present study,we determined whether the tumor necrosis factor apoptosis-inducing ligand(TRAIL)pathway was responsible for increased apoptosis of pDCs in hepatitis C virus(HCV)infection.We stimulated peripheral blood mononuclear cells(PBMCs)with recombinant HCV core protein within 12 hours to measure the relative expression of tumor necrosis factor apoptosis-inducing receptor 1(TRAIL-R1)and TRAIL-R2 in pDCs using flow cytometry and image cytometry.We also measured the relative expression of TRAIL in NK cells after stimulation with recombinant HCV core protein using flow cytometry and image cytometry.Using flow cytometry,our results show that within 12 hours of stimulation,HCV core protein increases TRAIL-R1 on pDCs by 0.01%,CD56 expression by 0.66%,and TRAIL expression by 0.66%,in NK cells as compared to unstimulated PBMCs.ELISA and fluorescence spectroscopy results showed that HCV core protein decreases Bcl-2 expression in PBMCs and in pDCs by 36%and 3%,respectively.Our results suggest that HCV core protein increases NK cell deletion of pDCs,independent of the Bcl-2 pathway,contributing to HCV viral escape from immune responses,which may result in chronic HCV infection.
