title: Enhanced inhibition of Avian leukosis virus subgroup J replication by multi-target miRNAs.
abstract: BACKGROUND
  Avian leukosis virus (ALV) is a major infectious disease that impacts the poultry industry worldwide. Despite intensive efforts, no effective vaccine has been developed against ALV because of mutations that lead to resistant forms. Therefore, there is a dire need to develop antiviral agents for the treatment of ALV infections and RNA interference (RNAi) is considered an effective antiviral strategy.
  
  
  RESULTS
  In this study, the avian leukosis virus subgroup J (ALV-J) proviral genome, including the gag genes, were treated as targets for RNAi. Four pairs of miRNA sequences were designed and synthesized that targeted different regions of the gag gene. The screened target (i.e., the gag genes) was shown to effectively suppress the replication of ALV-J by 19.0-77.3%. To avoid the generation of escape variants during virus infection, expression vectors of multi-target miRNAs were constructed using the multi-target serial strategy (against different regions of the gag, pol, and env genes). Multi-target miRNAs were shown to play a synergistic role in the inhibition of ALV-J replication, with an inhibition efficiency of viral replication ranging from 85.0-91.2%.
  
  
  CONCLUSIONS
  The strategy of multi-target miRNAs might be an effective method for inhibiting ALV replication and the acquisition of resistant mutations.
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No, 427 Maduan Street, Nangang District, Harbin 150001, People's Republic of China. mqw@hvri.ac.cn
authors.forename: Qing-Wen
authors.initials: QW
authors.lastname: Meng
authors.forename: Zai-Ping
authors.initials: ZP
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Tian
authors.forename: Zhi-Guang
authors.initials: ZG
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001353:Avian Leukosis / Q000821:virology; D001354:Avian Leukosis Virus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism; D015684:Gene Products, pol / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011201:Poultry Diseases / Q000821:virology; D034622:RNA Interference; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol; D035683:MicroRNAs