Frequent infection of human cancer xenografts with murine endogenous retroviruses in vivo

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:Blyth, Professor Karen and Cameron, Professor Ewan and Neil, Professor James and Bell, Mrs Margaret and Naseer, Dr Asif and Kilbey, Dr Anna and Gilroy, Dr Kathryn 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 > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of 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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
539151New Approaches to Modelling Human LeukaemiaJames NeilCancer Research UK (CAN-RES-UK)11951MVLS III - CENTRE FOR VIRUS RESEARCH