Roles as Potential Oncogene or Tumour Suppressor of the Midclustered MicroRNAs in Gallid Herpesvirus 2(GaHV2)-Induced Marek's Disease Lymphomagenesis
详细信息    查看官网全文
摘要
In the last decade,numerous of miRNAs have been identified in diverse virus families,particularly in herpesviruses.Gallid herpesvirus2(Ga HV2)is a representativeoncogenic alphaherpesvirus that induces rapid-onset T-cell lymphomas in its natural hosts namely Marek’s disease(MD).In Ga HV2 genome,the presence of26 mature miRNAs derived from 14 precursors assembled in three clusters,namely Meq-cluster,Mid-cluster and LAT-cluster,respectively.Several Ga HV2 miRNAs,especially for those in Meq-cluster(e.g.miR-M4),have been demonstrated to be critical for MD pathogenesis and/or tumourigenesis.The downstream Mid-cluster is regulated and transcribed by a same promoter of Meq-cluster,but the role of Mid-clustered miRNAs in Ga HV2 biology remains unclear.Presently,we have generated Mid-cluster and associated individual miRNA deletion mutants in GX0101 virus,a very virulent(vv)Ga HV2 strain.Using Ga HV2-infected chickens as animal models,we found that deletion of Mid-cluster significantly increased viral pathogenicity as unexpectedly.Compared to parental GX0101 virus,the individual deletion of miR-M1 and miR-M11separately increased the viral pathogenicity or oncogenecity while the individual deletion of miR-M31 significantly decreased the mortality and gross tumour incidence of virus infected chickens.Furthermore,our data confirms that in Ga HV2 infection,the viral oncogene meq is targeted and down-regulated by miR-M11-5p,a miR-M11-derived mature miRNA.To the best of our knowledge,this is the first report to present that the Mid-clustered miRNAs possibly act either as potential oncogene or tumour suppressor in MD lymphomagenesis.
In the last decade,numerous of mi RNAs have been identified in diverse virus families,particularly in herpesviruses.Gallid herpesvirus2(Ga HV2) is a representativeoncogenic alphaherpesvirus that induces rapid-onset T-cell lymphomas in its natural hosts namely Marek's disease(MD).In Ga HV2 genome,the presence of 26 mature mi RNAs derived from 14 precursors assembled in three clusters,namely Meq-cluster,Mid-cluster and LAT-cluster,respectively.Several Ga HV2 mi RNAs,especially for those in Meq-cluster(e.g.mi R-M4),have been demonstrated to be critical for MD pathogenesis and/or tumourigenesis.The downstream Mid-cluster is regulated and transcribed by a same promoter of Meq-cluster,but the role of Mid-clustered mi RNAs in Ga HV2 biology remains unclear.Presently,we have generated Mid-cluster and associated individual mi RNA deletion mutants in GX0101 virus,a very virulent(vv) Ga HV2 strain.Using Ga HV2-infected chickens as animal models,we found that deletion of Mid-cluster significantly increased viral pathogenicity as unexpectedly.Compared to parental GX0101 virus,the individual deletion of mi R-M1 and mi R-M11 separately increased the viral pathogenicity or oncogenecity while the individual deletion of mi R-M31 significantly decreased the mortality and gross tumour incidence of virus infected chickens.Furthermore,our data confirms that in Ga HV2 infection,the viral oncogene meq is targeted and down-regulated by mi R-M11-5p,a mi R-M11-derived mature mi RNA.To the best of our knowledge,this is the first report to present that the Mid-clustered mi RNAs possibly act either as potential oncogene or tumour suppressor in MD lymphomagenesis.
引文

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700