title: Frequent detection of infectious xenotropic murine leukemia virus (XMLV) in human cultures established from mouse xenografts.
abstract: OBJECTIVE
  To investigate the frequency of xenotropic murine leukemia virus (MLV) presence in human cell lines established from mouse xenografts and to search for the evidence of horizontal viral spread to other cell lines.
  
  
  RESULTS
  Six of 23 (26%) mouse DNA free xenograft cultures were strongly positive for MLV and their sequences had greater than 99% homology to known MLV strains. Four of five available supernatant fluids from these viral positive cultures were strongly positive for RT activity. Three of these supernatant fluids were studied to confirm the infectivity of the released virions for other human culture cells. Of the 78 non-xenograft derived cell lines maintained in the xenograft culture-containing facilities, 13 (17%) were positive for MLV, including XMRV, a virus strain first identified in human tissues. By contrast, all 50 cultures maintained in a xenograft culture-free facility were negative for viral sequences.
  
  
  METHODS
  We examined xenograft tumor cell lines from seven independent laboratories and 128 non-xenografted tumor cell lines. Cell line DNA was examined for mouse DNA contamination, and by 3 Taqman qPCR assays targeting the gag, env or pol regions of MLV. Sequencing was used for viral strain identification. Supernatant fluids were tested for reverse transcriptase (RT) activity.
  
  
  CONCLUSIONS
  Human cultures derived after mouse xenografting frequently contain and release highly infectious xenotropic MLV viruses. Laboratories working with xenograft-derived human cultures should be aware of the risk of contamination with potentially biohazardous human-tropic mouse viruses and their horizontal spread to other cultures.
authors.affiliation: Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Yu-An
authors.initials: YA
authors.lastname: Zhang
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rudin
authors.forename: Craig D
authors.initials: CD
authors.lastname: Peacock
authors.forename: Collins
authors.initials: C
authors.lastname: Karikari
authors.forename: Rolf A
authors.initials: RA
authors.lastname: Brekken
authors.forename: Victor
authors.initials: V
authors.lastname: Stastny
authors.forename: Boning
authors.initials: B
authors.lastname: Gao
authors.forename: Luc
authors.initials: L
authors.lastname: Girard
authors.forename: Ignacio
authors.initials: I
authors.lastname: Wistuba
authors.forename: Eugene
authors.initials: E
authors.lastname: Frenkel
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Adi F
authors.initials: AF
authors.lastname: Gazdar
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor / Q000821:virology*; D004247:DNA / Q000032:analysis; D018562:Disease Transmission, Infectious; D015752:Genes, env; D015750:Genes, gag; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity; D051379:Mice / Q000235:genetics; D012192:Retroviridae Infections / Q000635:transmission; D014183:Transplantation, Heterologous; D014771:Virion
chemical_list: D004247:DNA