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Viruses 2015, 7(4), 2014-2029;

Frequent Infection of Human Cancer Xenografts with Murine Endogenous Retroviruses in Vivo

Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK
School of Veterinary Medicine, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK
Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, G61 1BD Glasgow, UK
Present address: Khyber Medical University, PDA Building, Block IV, Phase 5, Hayatabad, Peshawar, Khyber Pakhtunkhwa, Pakistan.
Author to whom correspondence should be addressed.
Academic Editor: Welkin Johnson
Received: 15 December 2014 / Revised: 3 April 2015 / Accepted: 13 April 2015 / Published: 17 April 2015
(This article belongs to the Special Issue Endogenous Viruses)
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Infection of human cancer xenografts in mice with murine leukemia viruses (MLVs) is a long-standing observation, but the likelihood of infection in vivo and its biological consequences are poorly understood. We therefore conducted a prospective study in commonly used xenograft recipient strains. From BALB/c nude mice engrafted with MCF7 human mammary carcinoma cells, we isolated a virus that was virtually identical to Bxv1, a locus encoding replication-competent xenotropic MLV (XMLV). XMLV was detected in 9/17 (53%) independently isolated explants. XMLV was not found in primary leukemias or in THP1 leukemia cells grown in Bxv1-negative NSG (NOD/SCID/γCnull) mice, although MCF7 explants harbored replication-defective MLV proviruses. To assess the significance of infection for xenograft behavior in vivo, we examined changes in growth and global transcription in MCF7 and the highly susceptible Raji Burkitt lymphoma cell line chronically infected with XMLV. Raji cells showed a stronger transcriptional response that included up-regulation of chemokines and effectors of innate antiviral immunity. In conclusion, the risk of de novo XMLV infection of xenografts is high in Bxv1 positive mice, while infection can have positive or negative effects on xenograft growth potential with significant consequences for interpretation of many xenograft studies. View Full-Text
Keywords: xenograft; xenotropic; murine leukemia virus; cancer xenograft; xenotropic; murine leukemia virus; cancer

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Naseer, A.; Terry, A.; Gilroy, K.; Kilbey, A.; Watts, C.; Mackay, N.; Bell, M.; Mason, S.; Blyth, K.; Cameron, E.; Neil, J.C. Frequent Infection of Human Cancer Xenografts with Murine Endogenous Retroviruses in Vivo. Viruses 2015, 7, 2014-2029.

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