fulltext- https://www.landesbioscience.com/journals/cbt/ZhangCBT12-7.pdf
Supplemental materials can be found at:
www.landesbioscience.com/journals/cbt/article/15955/
Frequent detection of infectious xenotropic murine leukemia virus
(XMLV) in human cultures established from mouse xenografts
Cancer Biology and Therapy
Volume 12, Issue 7 October 1, 2011
Yu-An Zhang, Anirban Maitra, Jer-Tsong Hsieh, Charles M. Rudin, Craig
Peacock, Collins Karikari, Rolf A. Brekken, Victor Stastny, Boning
Gao, Luc Girard, Ignacio Wistuba, Eugene Frenkel, John D. Minna and
Adi F. Gazdar
Purpose: 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. Methodology: We examined xenograft tumor cell
lines from 7 independent laboratories and 128 non-xenografted tumor
cell lines. Cell line DNA was examined for mouse DNA contamination,
and by three 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. 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. 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.
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