title: Attenuation of the influenza virus by microRNA response element in vivo and protective efficacy against 2009 pandemic H1N1 virus in mice.
abstract: BACKGROUND
  The 2009 influenza pandemics underscored the need for effective vaccines to block the spread of influenza virus infection. Most live attenuated vaccines utilize cold-adapted, temperature-sensitive virus. An alternative to live attenuated virus is presented here, based on microRNA-induced gene silencing.
  
  
  METHODS
  In this study, miR-let-7b target sequences were inserted into the H1N1 genome to engineer a recombinant virus - miRT-H1N1. Female BALB/c mice were vaccinated intranasally with the miRT-H1N1 and challenged with a lethal dose of homologous virus.
  
  
  RESULTS
  This miRT-H1N1 virus was attenuated in mice, while it exhibited wild-type characteristics in chicken embryos. Mice vaccinated intranasally with the miRT-H1N1 responded with robust immunity that protected the vaccinated mice from a lethal challenge with the wild-type 2009 pandemic H1N1 virus.
  
  
  CONCLUSIONS
  These results indicate that the influenza virus containing microRNA response elements (MREs) is attenuated in vivo and can be used to design a live attenuated vaccine.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital affiliated to Southern Medical University, Nanjing, China.
authors.forename: Chunlai
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital affiliated to Southern Medical University, Nanjing, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital affiliated to Southern Medical University, Nanjing, China.
authors.forename: Wenkui
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital affiliated to Southern Medical University, Nanjing, China. Electronic address: shiyi56@126.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: The Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing, China; Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Minnesota at Twin Cities, Saint Paul, Minnesota, USA. Electronic address: zxing@umn.edu.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xing
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002642:Chick Embryo; D005260:Female; D006801:Humans; D007109:Immunity / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology; D007251:Influenza, Human / Q000453:epidemiology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D058873:Pandemics; D020218:Response Elements; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D035683:MicroRNAs; D014613:Vaccines, Attenuated
keywords: H1N1; Immunogenicity; Influenza; Live attenuated vaccine