Ebola virus(EBOV),a member of the filovirus family,is an enveloped negative-sense RNA virus that causes lethal infections in humans and primates.Recently,more than 1000 people have been killed by the Ebola virus disea...Ebola virus(EBOV),a member of the filovirus family,is an enveloped negative-sense RNA virus that causes lethal infections in humans and primates.Recently,more than 1000 people have been killed by the Ebola virus disease in Africa,yet no specific treatment or diagnostic tests for EBOV are available.In this study,we identified two putative viral microRNA precursors(pre-miRNAs)and three putative mature microRNAs(miRNAs)derived from the EBOV genome.The production of the EBOV miRNAs was further validated in HEK293T cells transfected with a pcDNA6.2-GW/EmGFP-EBOV-pre-miRNA plasmid,indicating that EBOV miRNAs can be produced through the cellular miRNA processing machinery.We also predicted the potential target genes of these EBOV miRNAs and their possible biological functions.Overall,this study reports for the first time that EBOV may produce miRNAs,which could serve as non-invasive biomarkers for the diagnosis and prognosis of EBOV infection and as therapeutic targets for Ebola viral infection treatment.展开更多
Ebola virus(EBOV)causes a highly lethal hemorrhagic fever syndrome in humans and has been associated with mortality rates of up to 91%in Zaire,the most lethal strain.Though the viral envelope glycoprotein(GP)mediates ...Ebola virus(EBOV)causes a highly lethal hemorrhagic fever syndrome in humans and has been associated with mortality rates of up to 91%in Zaire,the most lethal strain.Though the viral envelope glycoprotein(GP)mediates widespread inflammation and cellular damage,these changes have mainly focused on alterations at the protein level,the role of microRNAs(miRNAs)in the molecular pathogenesis underlying this lethal disease is not fully understood.Here,we report that the miRNAs hsa-miR-1246,hsa-miR-320a and hsa-miR-196b-5p were induced in human umbilical vein endothelial cells(HUVECs)following expression of EBOV GP.Among the proteins encoded by predicted targets of these miRNAs,the adhesion-related molecules tissue factor pathway inhibitor(TFPI),dystroglycan1(DAG1)and the caspase 8 and FADD-like apoptosis regulator(CFLAR)were significantly downregulated in EBOV GP-expressing HUVECs.Moreover,inhibition of hsa-miR-1246,hsa-miR-320a and hsa-miR-196b-5p,or overexpression of TFPI,DAG1 and CFLAR rescued the cell viability that was induced by EBOV GP.Our results provide a novel molecular basis for EBOV pathogenesis and may contribute to the development of strategies to protect against future EBOV pandemics.展开更多
目的探讨慢性乙型肝炎(chronic hepatitis B,CHB)患者微小RNA-223(microRNA-223,miR-223)、高迁移率族蛋白B1(high mobility group box-1 protein,HMGB1)表达水平及其与乙型肝炎病毒(hepatitis B virus,HBV)DNA载量及肝功能的关系。方...目的探讨慢性乙型肝炎(chronic hepatitis B,CHB)患者微小RNA-223(microRNA-223,miR-223)、高迁移率族蛋白B1(high mobility group box-1 protein,HMGB1)表达水平及其与乙型肝炎病毒(hepatitis B virus,HBV)DNA载量及肝功能的关系。方法选取本院收治的86例CHB患者为CHB组和78例健康体检者为对照组。测定HBV-DNA载量并分析CHB患者miR-223、HMGB1与肝功能指标的相关性及影响CHB发生的因素。结果CHB组miR-223、HMGB1、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、谷氨酰转移酶(GGT)、总胆红素(TBIL)高于对照组(P<0.05)。HBV-DNA高载量组miR-223、HMGB1高于HBV-DNA中载量组、HBV-DNA低载量组(P<0.05)。CHB患者miR-223与HMGB1呈正相关(P<0.05),二者与ALT、AST、GGT、TBIL均呈正相关(P<0.05)。miR-223、HMGB1、HBV-DNA载量是影响CHB发生的独立危险因素(P<0.05)。结论miR-223、HMGB1可一定程度反映CHB患者HBV-DNA载量及肝功能。展开更多
基金supported by the National Basic Research Program of China(2014CB542300)the National Natural Science Foundation of China(81101330,31271378,81250044)+2 种基金the Natural Science Foundation of Jiangsu Province(BK2012014)the Research Special Fund for Public Welfare Industry of Health(201302018)supported by the Program for New Century Excellent Talents in University from Ministry of Education of China(NCET-12-0261)
文摘Ebola virus(EBOV),a member of the filovirus family,is an enveloped negative-sense RNA virus that causes lethal infections in humans and primates.Recently,more than 1000 people have been killed by the Ebola virus disease in Africa,yet no specific treatment or diagnostic tests for EBOV are available.In this study,we identified two putative viral microRNA precursors(pre-miRNAs)and three putative mature microRNAs(miRNAs)derived from the EBOV genome.The production of the EBOV miRNAs was further validated in HEK293T cells transfected with a pcDNA6.2-GW/EmGFP-EBOV-pre-miRNA plasmid,indicating that EBOV miRNAs can be produced through the cellular miRNA processing machinery.We also predicted the potential target genes of these EBOV miRNAs and their possible biological functions.Overall,this study reports for the first time that EBOV may produce miRNAs,which could serve as non-invasive biomarkers for the diagnosis and prognosis of EBOV infection and as therapeutic targets for Ebola viral infection treatment.
基金supported by the National Natural Science Foundation of China(81230002,81300057,91019016,31361163004)National Basic Research Program of China(2012CB316503)+3 种基金Ministry of Health(201302017)Ministry of Science and Technology of China(2006AA02Z152)Program of Introducing Talents of Discipline to Universities(B08007)the support of the Science and Technology Commission of Shanghai Municipality(07pj14096)
文摘Ebola virus(EBOV)causes a highly lethal hemorrhagic fever syndrome in humans and has been associated with mortality rates of up to 91%in Zaire,the most lethal strain.Though the viral envelope glycoprotein(GP)mediates widespread inflammation and cellular damage,these changes have mainly focused on alterations at the protein level,the role of microRNAs(miRNAs)in the molecular pathogenesis underlying this lethal disease is not fully understood.Here,we report that the miRNAs hsa-miR-1246,hsa-miR-320a and hsa-miR-196b-5p were induced in human umbilical vein endothelial cells(HUVECs)following expression of EBOV GP.Among the proteins encoded by predicted targets of these miRNAs,the adhesion-related molecules tissue factor pathway inhibitor(TFPI),dystroglycan1(DAG1)and the caspase 8 and FADD-like apoptosis regulator(CFLAR)were significantly downregulated in EBOV GP-expressing HUVECs.Moreover,inhibition of hsa-miR-1246,hsa-miR-320a and hsa-miR-196b-5p,or overexpression of TFPI,DAG1 and CFLAR rescued the cell viability that was induced by EBOV GP.Our results provide a novel molecular basis for EBOV pathogenesis and may contribute to the development of strategies to protect against future EBOV pandemics.
文摘目的探讨慢性乙型肝炎(chronic hepatitis B,CHB)患者微小RNA-223(microRNA-223,miR-223)、高迁移率族蛋白B1(high mobility group box-1 protein,HMGB1)表达水平及其与乙型肝炎病毒(hepatitis B virus,HBV)DNA载量及肝功能的关系。方法选取本院收治的86例CHB患者为CHB组和78例健康体检者为对照组。测定HBV-DNA载量并分析CHB患者miR-223、HMGB1与肝功能指标的相关性及影响CHB发生的因素。结果CHB组miR-223、HMGB1、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、谷氨酰转移酶(GGT)、总胆红素(TBIL)高于对照组(P<0.05)。HBV-DNA高载量组miR-223、HMGB1高于HBV-DNA中载量组、HBV-DNA低载量组(P<0.05)。CHB患者miR-223与HMGB1呈正相关(P<0.05),二者与ALT、AST、GGT、TBIL均呈正相关(P<0.05)。miR-223、HMGB1、HBV-DNA载量是影响CHB发生的独立危险因素(P<0.05)。结论miR-223、HMGB1可一定程度反映CHB患者HBV-DNA载量及肝功能。
