title: Attenuated reovirus displays oncolysis with reduced host toxicity.
abstract: BACKGROUND
  Although the naturally occurring reovirus causes only mild symptoms in humans, it shows considerable potential as an oncolytic agent because of its innate ability to target cancer cells. In immunocompromised hosts, however, wild-type reovirus can target healthy tissues, including heart, liver, pancreas and neural structures.
  
  
  METHODS
  We characterized an attenuated form of reovirus (AV) derived from a persistently infected cell line through sequence analysis, as well as western blot and in vitro transcription and translation techniques. To examine its pathogenesis and oncolytic potential, AV reovirus was tested on healthy embryonic stem cells, various non-transformed and transformed cell lines, and in severe combined immunodeficiency (SCID) mice with tumour xenografts.
  
  
  RESULTS
  Sequence analysis of AV reovirus revealed a premature STOP codon in its sigma 1 attachment protein. Western blot and in vitro translation confirmed the presence of a truncated σ1. In comparison to wild-type reovirus, AV reovirus did not kill healthy stem cells or induce black tail formation in SCID mice. However, it did retain its ability to target cancer cells and reduce tumour size.
  
  
  CONCLUSIONS
  Despite containing a truncated attachment protein, AV reovirus still preferentially targets cancer cells, and compared with wild-type reovirus it shows reduced toxicity when administered to immunodeficient hosts, suggesting the potential use of AV reovirus in combination cancer therapy.
authors.affiliation: Department of Medical Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.forename: K A
authors.initials: KA
authors.lastname: Garant
authors.forename: N I
authors.initials: NI
authors.lastname: zur Nieden
authors.forename: T
authors.initials: T
authors.lastname: Alain
authors.forename: S D
authors.initials: SD
authors.lastname: Loken
authors.forename: S J
authors.initials: SJ
authors.lastname: Urbanski
authors.forename: P A
authors.initials: PA
authors.lastname: Forsyth
authors.forename: D E
authors.initials: DE
authors.lastname: Rancourt
authors.forename: P W K
authors.initials: PW
authors.lastname: Lee
authors.forename: R N
authors.initials: RN
authors.lastname: Johnston
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D008854:Microscopy, Electron; D050130:Oncolytic Virotherapy; D014176:Protein Biosynthesis; D012087:Reoviridae / Q000235:genetics / Q000472:pathogenicity*; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous; D014774:Virulence
chemical_list: D017931:DNA Primers