We conducted genome sequence analysis to examine the presence/absence of two types of Z-DNA binding domains in various organisms. We examined 68 organisms from archaea, 914 organisms from bacteria, and 199 organisms f...We conducted genome sequence analysis to examine the presence/absence of two types of Z-DNA binding domains in various organisms. We examined 68 organisms from archaea, 914 organisms from bacteria, and 199 organisms from eukaryotes. RecA protein from Escherichia coli has a Z-DNA binding domain and this protein promotes homologous recombination. All the organisms examined had this domain. This result indicated that this domain is essential for all the organisms. RNA editing enzyme, adenosine deaminase from human has another type of Z-DNA binding domain. This domain was observed in some organisms of archaea, bacteria, and eukaryotes. The presence/absence of Z-DNA binding domain in adenosine deaminase indicated that gain and loss of this domain had occurred in the process of evolution. The implication of presence and absence of this domain is discussed in this study.展开更多
VP22是一种保守的被膜蛋白,广泛存在于伪狂犬病病毒(PRV)和HSV-1等α-疱疹病毒中。HSV-1的VP22是病毒的重要毒力因子,它通过调节病毒蛋白和宿主蛋白的亚细胞定位,增强病毒的神经毒性;HSV-1 VP22还能够抑制AIM2炎症小体的激活,进而促进...VP22是一种保守的被膜蛋白,广泛存在于伪狂犬病病毒(PRV)和HSV-1等α-疱疹病毒中。HSV-1的VP22是病毒的重要毒力因子,它通过调节病毒蛋白和宿主蛋白的亚细胞定位,增强病毒的神经毒性;HSV-1 VP22还能够抑制AIM2炎症小体的激活,进而促进病毒的复制。然而,PRV VP22与HSV-1 VP22的同源性仅为26%,其在病毒感染和致病中的作用尚不明确。近期,mBio杂志发表了题为“Suppression of ZBP1-mediated NLRP3 inflammasome by the tegument protein VP22 facilitates pseudorabies virus infection”的研究论文,论文的通讯作者为南京农业大学动物医学院姜平教授和刘星教授,第一作者为博士后马梓承。本研究揭示了ZBP1介导的NLRP3炎症小体在PRV感染中的作用,并发现PRV VP22通过抑制该途径介导的炎症反应,促进病毒的复制和致病性。该研究成果为理解PRV复制和致病机制提供了新的视角。展开更多
Background:Sepsis is often accompanied by lactic acidemia and acute lung injury(ALI).Clinical studies have established that high serum lactate levels are associated with increased mortality rates in septic patients.We...Background:Sepsis is often accompanied by lactic acidemia and acute lung injury(ALI).Clinical studies have established that high serum lactate levels are associated with increased mortality rates in septic patients.We further observed a significant correlation between the levels of cold-inducible RNA-binding protein(CIRP)in plasma and bronchoalveolar lavage fluid(BALF),as well as lactate levels,and the severity of post-sepsis ALI.The underlying mechanism,however,remains elusive.Methods:C57BL/6 wild type(WT),Casp8^(-/-),Ripk3^(-/-),and Zbp1^(-/-)mice were subjected to the cecal ligation and puncture(CLP)sepsis model.In this model,we measured intra-macrophage CIRP lactylation and the subsequent release of CIRP.We also tracked the internalization of extracellular CIRP(eCIRP)in pulmonary vascular endothelial cells(PVECs)and its interaction with Z-DNA binding protein 1(ZBP1).Furthermore,we monitored changes in ZBP1 levels in PVECs and the consequent activation of cell death pathways.Results:In the current study,we demonstrate that lactate,accumulating during sepsis,promotes the lactylation of CIRP in macrophages,leading to the release of CIRP.Once eCIRP is internalized by PVEC through a Toll-like receptor 4(TLR4)-mediated endocytosis pathway,it competitively binds to ZBP1 and effectively blocks the interaction between ZBP1 and tripartite motif containing 32(TRIM32),an E3 ubiquitin ligase targeting ZBP1 for proteasomal degradation.This interference mechanism stabilizes ZBP1,thereby enhancing ZBP1-receptor-interacting protein kinase 3(RIPK3)-dependent PVEC PANoptosis,a form of cell death involving the simultaneous activation of multiple cell death pathways,thereby exacerbating ALI.Conclusions:These findings unveil a novel pathway by which lactic acidemia promotes macrophage-derived eCIRP release,which,in turn,mediates ZBP1-dependent PVEC PANoptosis in sepsis-induced ALI.This finding offers new insights into the molecular mechanisms driving sepsis-related pulmonary complications and provides potential new therapeutic strategies.展开更多
文摘We conducted genome sequence analysis to examine the presence/absence of two types of Z-DNA binding domains in various organisms. We examined 68 organisms from archaea, 914 organisms from bacteria, and 199 organisms from eukaryotes. RecA protein from Escherichia coli has a Z-DNA binding domain and this protein promotes homologous recombination. All the organisms examined had this domain. This result indicated that this domain is essential for all the organisms. RNA editing enzyme, adenosine deaminase from human has another type of Z-DNA binding domain. This domain was observed in some organisms of archaea, bacteria, and eukaryotes. The presence/absence of Z-DNA binding domain in adenosine deaminase indicated that gain and loss of this domain had occurred in the process of evolution. The implication of presence and absence of this domain is discussed in this study.
文摘VP22是一种保守的被膜蛋白,广泛存在于伪狂犬病病毒(PRV)和HSV-1等α-疱疹病毒中。HSV-1的VP22是病毒的重要毒力因子,它通过调节病毒蛋白和宿主蛋白的亚细胞定位,增强病毒的神经毒性;HSV-1 VP22还能够抑制AIM2炎症小体的激活,进而促进病毒的复制。然而,PRV VP22与HSV-1 VP22的同源性仅为26%,其在病毒感染和致病中的作用尚不明确。近期,mBio杂志发表了题为“Suppression of ZBP1-mediated NLRP3 inflammasome by the tegument protein VP22 facilitates pseudorabies virus infection”的研究论文,论文的通讯作者为南京农业大学动物医学院姜平教授和刘星教授,第一作者为博士后马梓承。本研究揭示了ZBP1介导的NLRP3炎症小体在PRV感染中的作用,并发现PRV VP22通过抑制该途径介导的炎症反应,促进病毒的复制和致病性。该研究成果为理解PRV复制和致病机制提供了新的视角。
基金supported by grants from the USA VA(1I01BX004838 and IK6BX006297)the Shenzhen Science and Technology Program(JCYJ20230807142311024).
文摘Background:Sepsis is often accompanied by lactic acidemia and acute lung injury(ALI).Clinical studies have established that high serum lactate levels are associated with increased mortality rates in septic patients.We further observed a significant correlation between the levels of cold-inducible RNA-binding protein(CIRP)in plasma and bronchoalveolar lavage fluid(BALF),as well as lactate levels,and the severity of post-sepsis ALI.The underlying mechanism,however,remains elusive.Methods:C57BL/6 wild type(WT),Casp8^(-/-),Ripk3^(-/-),and Zbp1^(-/-)mice were subjected to the cecal ligation and puncture(CLP)sepsis model.In this model,we measured intra-macrophage CIRP lactylation and the subsequent release of CIRP.We also tracked the internalization of extracellular CIRP(eCIRP)in pulmonary vascular endothelial cells(PVECs)and its interaction with Z-DNA binding protein 1(ZBP1).Furthermore,we monitored changes in ZBP1 levels in PVECs and the consequent activation of cell death pathways.Results:In the current study,we demonstrate that lactate,accumulating during sepsis,promotes the lactylation of CIRP in macrophages,leading to the release of CIRP.Once eCIRP is internalized by PVEC through a Toll-like receptor 4(TLR4)-mediated endocytosis pathway,it competitively binds to ZBP1 and effectively blocks the interaction between ZBP1 and tripartite motif containing 32(TRIM32),an E3 ubiquitin ligase targeting ZBP1 for proteasomal degradation.This interference mechanism stabilizes ZBP1,thereby enhancing ZBP1-receptor-interacting protein kinase 3(RIPK3)-dependent PVEC PANoptosis,a form of cell death involving the simultaneous activation of multiple cell death pathways,thereby exacerbating ALI.Conclusions:These findings unveil a novel pathway by which lactic acidemia promotes macrophage-derived eCIRP release,which,in turn,mediates ZBP1-dependent PVEC PANoptosis in sepsis-induced ALI.This finding offers new insights into the molecular mechanisms driving sepsis-related pulmonary complications and provides potential new therapeutic strategies.
