本文旨在探究富含天冬氨酸尾1的单通道膜蛋白(Single-pass Membrane Protein With Aspartate Rich Tail1,Smdt1)对C3H10T1/2细胞增殖和成脂分化的调控效应。本研究将Smdt1基因的过表达和干扰载体转染至C3H10T1/2细胞模型,采用qPCR方法...本文旨在探究富含天冬氨酸尾1的单通道膜蛋白(Single-pass Membrane Protein With Aspartate Rich Tail1,Smdt1)对C3H10T1/2细胞增殖和成脂分化的调控效应。本研究将Smdt1基因的过表达和干扰载体转染至C3H10T1/2细胞模型,采用qPCR方法量化了增殖和成脂分化关键基因的表达水平变化,利用EdU染色检测细胞增殖活力,油红O染色方法鉴定脂滴积累的状态;进一步通过String database、Bio GRID、Int Act、GeneMANIA、DAVID和Genecard数据库构建Smdt1蛋白互作网络图。结果显示,在C3H10T1/2细胞中过表达Smdt1,极显著提升了增殖标志基因Pcna、Ki67、Cdk1及Cdk4的表达,EdU阳性细胞比例反映了细胞增殖速率加快;Smdt1极显著促进成脂分化关键基因Pparγ、Fabp4、-Adipoq的表达量,显著促进了Cebpα、Cebpβ的表达量,脂滴数量变多。在C3H10T1/2细胞体系中,干扰Smdt1,与增殖紧密相关的标志基因,包括Ki67、Pcna及Cdk1,其表达水平极显著降低,Cdk4的表达也呈现显著降低的趋势,反映在EdU增殖检测中,阳性细胞数量明显减少,细胞增殖活性受到抑制。进一步干扰Smdt1后,成脂分化途径的关键调控基因Cebpα、Pparγ、Cebpβ、Fabp4、Adipoq的表达均极显著降低,细胞内脂滴的数量也显著减少,细胞成脂分化能力削弱。蛋白功能预测发现,Smdt1能够与Mcu相互作用,参与线粒体钙离子转运、摄取和稳态。本研究发现Smdt1可以促进C3H10T1/2细胞增殖和成脂分化,为脂肪沉积的研究提供了新的方向。展开更多
On January 30,2024,China announced the first human case of H10N5 influenza infection.Prior to this,human cases of H10N7 and H10N8 had been reported.It is now appropriate to re-examine the evolution and future epidemio...On January 30,2024,China announced the first human case of H10N5 influenza infection.Prior to this,human cases of H10N7 and H10N8 had been reported.It is now appropriate to re-examine the evolution and future epidemiological trends of the H10 and N5 subtypes of avian influenza viruses(AIVs).In this study,we analyzed the reassortment characteristics of the first human-derived H10N5 AIV(A/Zhejiang/ZJU01/2023),as well as the evolutionary dynamics of the wild bird-derived H10 and N5 subtypes of AIVs over the past decade.Our findings indicate that the human-derived H10N5 AIV exhibited low pathogenicity.A/bean_goose/Korea/KNU-10/2022(H10N7)and A/mallard/Novosibirsk_region/962k/2018(H12N5)were identified as the potential reassortment parents.The virus has existed since 2022 and several isolations have been reported in Bangladesh.Phylogenetic analysis showed that H10Ny and HxN5 AIVs in China are clustered differently based on the East Asian-Australian(eastern)and Central Asian-Indian(western)migratory flyways.The H10Ny and HxN5 AIV reassortant strains may cause human infections through accidental spillover.It is possible that another center of AIV evolution,mutation,and reassortment may be developing along the migratory flyways in northeastern Asia,distinct from Europe,the Americas,and China's Yangtze River Delta and Pearl River Delta,which should be closely monitored to ensure the safety of the public.展开更多
The H10 subtype avian influenza virus(AIV)poses an ongoing threat to both birds and humans.Notably,fatal human cases of H10N3 and H10N8 infections have drawn public attention.In 2022,we isolated two H10N3 viruses(A/ch...The H10 subtype avian influenza virus(AIV)poses an ongoing threat to both birds and humans.Notably,fatal human cases of H10N3 and H10N8 infections have drawn public attention.In 2022,we isolated two H10N3 viruses(A/chicken/Shandong/0101/2022 and A/chicken/Shandong/0603/2022)from diseased chickens in China.Genome analysis revealed that these viruses were genetically associated with human-origin H10N3 virus,with internal genes originating from local H9N2 viruses.Compared to the H10N8 virus(A/chicken/Jiangxi/102/2013),the H10N3 viruses exhibited enhanced thermostability,increased viral release from erythrocytes,and accumulation of hemagglutinin(HA)protein.Additionally,we evaluated the pathogenicity of both H10N3 and H10N8 viruses in mice.We found that viral titers could be detected in the lungs and nasal turbinates of mice infected with the two H10N3 viruses,whereas H10N8 virus titers were detectable in the lungs and brains of mice.Notably,the proportion of double HA Q222R and G228S mutations in H10N3 viruses has increased since 2019.However,the functional roles of the Q222R and G228S double mutations in the HA gene of H10N3 viruses remain unknown and warrant further investigation.Our study highlights the potential public health risk posed by the H10N3 virus.A spillover event of AIV to humans could be a foretaste of a looming pandemic.Therefore,it is imperative to continuously monitor the evolution of the H10N3 influenza virus to ensure targeted prevention and control measures against influenza outbreaks.展开更多
H10 subtype avian influenza viruses(AIV)have been circulating in China for 40 years.H10 AIVs in China have expanded their host range from wild birds to domestic poultry and mammals,even human.Most of the H10 subtype A...H10 subtype avian influenza viruses(AIV)have been circulating in China for 40 years.H10 AIVs in China have expanded their host range from wild birds to domestic poultry and mammals,even human.Most of the H10 subtype AIVs reported in China were isolate from the southeast part.We isolated an H10N3 AIV,A/Chicken/Liaoning/SY1080/2021(SY1080),from live poultry market(LPM)in Liaoning Province of the Northeast China.SY1080replicated efficiently in mice lungs and nasal turbinates without prior adaptation.We systematically compared SY1080 with other H10 subtype isolates in China.Phylogenetic analysis showed that SY1080 and most of the H10strains belonged to the Eurasian lineage.H10 AIVs in China have formed 63 genotypes.SY1080 as well as the H10N3 strains from human infections belonged to G60 genotype.H10Nx AIV acquired multiple mammalian adaptive and virulence related mutations during circulation and the recent reassortants derived internal genes from chicken H9N2 AIVs.The H10Nx subtypes AIVs posed potential threat to public health.These results suggested we should strengthen the surveillance and evaluation of H10 subtype strains.展开更多
文摘本文旨在探究富含天冬氨酸尾1的单通道膜蛋白(Single-pass Membrane Protein With Aspartate Rich Tail1,Smdt1)对C3H10T1/2细胞增殖和成脂分化的调控效应。本研究将Smdt1基因的过表达和干扰载体转染至C3H10T1/2细胞模型,采用qPCR方法量化了增殖和成脂分化关键基因的表达水平变化,利用EdU染色检测细胞增殖活力,油红O染色方法鉴定脂滴积累的状态;进一步通过String database、Bio GRID、Int Act、GeneMANIA、DAVID和Genecard数据库构建Smdt1蛋白互作网络图。结果显示,在C3H10T1/2细胞中过表达Smdt1,极显著提升了增殖标志基因Pcna、Ki67、Cdk1及Cdk4的表达,EdU阳性细胞比例反映了细胞增殖速率加快;Smdt1极显著促进成脂分化关键基因Pparγ、Fabp4、-Adipoq的表达量,显著促进了Cebpα、Cebpβ的表达量,脂滴数量变多。在C3H10T1/2细胞体系中,干扰Smdt1,与增殖紧密相关的标志基因,包括Ki67、Pcna及Cdk1,其表达水平极显著降低,Cdk4的表达也呈现显著降低的趋势,反映在EdU增殖检测中,阳性细胞数量明显减少,细胞增殖活性受到抑制。进一步干扰Smdt1后,成脂分化途径的关键调控基因Cebpα、Pparγ、Cebpβ、Fabp4、Adipoq的表达均极显著降低,细胞内脂滴的数量也显著减少,细胞成脂分化能力削弱。蛋白功能预测发现,Smdt1能够与Mcu相互作用,参与线粒体钙离子转运、摄取和稳态。本研究发现Smdt1可以促进C3H10T1/2细胞增殖和成脂分化,为脂肪沉积的研究提供了新的方向。
基金funded by the National Natural Science Foundation of China(81872673)the Shanghai New Three-year Action Plan for Public Health(GWVI-11.1-03).
文摘On January 30,2024,China announced the first human case of H10N5 influenza infection.Prior to this,human cases of H10N7 and H10N8 had been reported.It is now appropriate to re-examine the evolution and future epidemiological trends of the H10 and N5 subtypes of avian influenza viruses(AIVs).In this study,we analyzed the reassortment characteristics of the first human-derived H10N5 AIV(A/Zhejiang/ZJU01/2023),as well as the evolutionary dynamics of the wild bird-derived H10 and N5 subtypes of AIVs over the past decade.Our findings indicate that the human-derived H10N5 AIV exhibited low pathogenicity.A/bean_goose/Korea/KNU-10/2022(H10N7)and A/mallard/Novosibirsk_region/962k/2018(H12N5)were identified as the potential reassortment parents.The virus has existed since 2022 and several isolations have been reported in Bangladesh.Phylogenetic analysis showed that H10Ny and HxN5 AIVs in China are clustered differently based on the East Asian-Australian(eastern)and Central Asian-Indian(western)migratory flyways.The H10Ny and HxN5 AIV reassortant strains may cause human infections through accidental spillover.It is possible that another center of AIV evolution,mutation,and reassortment may be developing along the migratory flyways in northeastern Asia,distinct from Europe,the Americas,and China's Yangtze River Delta and Pearl River Delta,which should be closely monitored to ensure the safety of the public.
基金supported by the National Natural Science Foundation of China(32330104,32302956)the China Postdoctoral Science Foundation(2023T160252,Jiahao Zhang)+1 种基金the Guangzhou Science and Technology Plan Project(SL2022B03J01423)the Changjiang Distinguished Professor Program(2023,Wenbao Qi).
文摘The H10 subtype avian influenza virus(AIV)poses an ongoing threat to both birds and humans.Notably,fatal human cases of H10N3 and H10N8 infections have drawn public attention.In 2022,we isolated two H10N3 viruses(A/chicken/Shandong/0101/2022 and A/chicken/Shandong/0603/2022)from diseased chickens in China.Genome analysis revealed that these viruses were genetically associated with human-origin H10N3 virus,with internal genes originating from local H9N2 viruses.Compared to the H10N8 virus(A/chicken/Jiangxi/102/2013),the H10N3 viruses exhibited enhanced thermostability,increased viral release from erythrocytes,and accumulation of hemagglutinin(HA)protein.Additionally,we evaluated the pathogenicity of both H10N3 and H10N8 viruses in mice.We found that viral titers could be detected in the lungs and nasal turbinates of mice infected with the two H10N3 viruses,whereas H10N8 virus titers were detectable in the lungs and brains of mice.Notably,the proportion of double HA Q222R and G228S mutations in H10N3 viruses has increased since 2019.However,the functional roles of the Q222R and G228S double mutations in the HA gene of H10N3 viruses remain unknown and warrant further investigation.Our study highlights the potential public health risk posed by the H10N3 virus.A spillover event of AIV to humans could be a foretaste of a looming pandemic.Therefore,it is imperative to continuously monitor the evolution of the H10N3 influenza virus to ensure targeted prevention and control measures against influenza outbreaks.
基金supported by the National Key Research and Development Program of China(2021YFD1800200)the National Natural Science Foundation of China(32170539,32000357)Liaoning Revitalization Talents Program,China(XLYC2007114)。
文摘H10 subtype avian influenza viruses(AIV)have been circulating in China for 40 years.H10 AIVs in China have expanded their host range from wild birds to domestic poultry and mammals,even human.Most of the H10 subtype AIVs reported in China were isolate from the southeast part.We isolated an H10N3 AIV,A/Chicken/Liaoning/SY1080/2021(SY1080),from live poultry market(LPM)in Liaoning Province of the Northeast China.SY1080replicated efficiently in mice lungs and nasal turbinates without prior adaptation.We systematically compared SY1080 with other H10 subtype isolates in China.Phylogenetic analysis showed that SY1080 and most of the H10strains belonged to the Eurasian lineage.H10 AIVs in China have formed 63 genotypes.SY1080 as well as the H10N3 strains from human infections belonged to G60 genotype.H10Nx AIV acquired multiple mammalian adaptive and virulence related mutations during circulation and the recent reassortants derived internal genes from chicken H9N2 AIVs.The H10Nx subtypes AIVs posed potential threat to public health.These results suggested we should strengthen the surveillance and evaluation of H10 subtype strains.
文摘2013年,从秦皇岛野鸟林鹬体内分离到一株H10N7亚型禽流感病毒(AIV),命名为A/Wood Sandpiper/Qinhuangdao/660-662/2013(H10N7)[简称WSP/QHD/660-662/2013(H10N7)]。本研究对该分离株的全基因序列进行测定,并对其进行致病性研究。基因组序列分析表明:该病毒的HA蛋白裂解位点为334PELMQGRGL343,属于低致病性AIV的分子特征,其HA基因与A/Duck/Hunan/S11205/2012(H10N3)的相似性达到97.90%,NA基因与A/Domestic Duck/Republic of Georgia/1/2010(H10N7)的相似性达到97.46%,内部基因与H9N2等多亚型AIV的相应基因节段具有较高的相似性,推测该分离株可能为一株多亚型流感病毒的重组株。对动物致病性试验结果显示:该病毒可以感染哺乳动物模型BALB/c小鼠,并且仅能够在鼠的肺脏和鼻甲骨粘膜上皮细胞中复制,表明该病毒分离株对小鼠也呈现低致病性。
