Naseer, A. et al. (2015) Frequent infection of human cancer xenografts with murine endogenous retroviruses in vivo. Viruses, 7(4), pp. 2014-2029. (doi: 10.3390/v7042014) (PMID:25912714) (PMCID:PMC4411688)
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Abstract
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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Bell, Mrs Margaret and Blyth, Professor Karen and Cameron, Professor Ewan and Naseer, Dr Asif and Kilbey, Dr Anna and Gilroy, Dr Kathryn and Neil, Professor James and Mason, Miss Susan and Watts, Dr Ciorsdaidh and Terry, Mrs Anne |
| Authors: | Naseer, A., Terry, A., Gilroy, K., Kilbey, A., Watts, C., Mackay, N., Bell, M., Mason, S., Blyth, K., Cameron, E., and Neil, J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | Viruses |
| Publisher: | MDPI AG |
| ISSN: | 1999-4915 |
| ISSN (Online): | 1999-4915 |
| Copyright Holders: | Copyright © 2014 The Authors |
| First Published: | First published in Viruses 7(4):2014-2029 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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