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Authors: Yu-An Zhang, Anirban Maitra, Jer-Tsong Hsieh, Charles M. Rudin, Craig D. Peacock, Collins Karikari, Rolf A. Brekken, Victor Stastny, Boning Gao, Luc Girard, Ignacio Wistuba, Eugene Frenkel, John D. Minna and Adi F. Gazdar

Yu-An Zhang

The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

Anirban Maitra

Johns Hopkins University School of Medicine, Baltimore, MD, USA

Jer-Tsong Hsieh

The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

Charles M. Rudin

Johns Hopkins University School of Medicine, Baltimore, MD, USA

Craig D. Peacock

Johns Hopkins University School of Medicine, Baltimore, MD, USA

Collins Karikari

Johns Hopkins University School of Medicine, Baltimore, MD, USA

Rolf A. Brekken

The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

Victor Stastny

The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

Boning Gao

The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

Luc Girard

The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

Ignacio Wistuba

MD Anderson Cancer Center, Houston, TX, USA

Eugene Frenkel

The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

John D. Minna

The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

Adi F. Gazdar

Corresponding author: adi.gazdar@utsouthwestern.edu
The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

Abstract:
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.

Received: April 15, 2011; Accepted: June 22, 2011

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