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Restoration of endogenous retrovirus infectivity impacts mouse cancer models

(2018) CANCER IMMUNOLOGY RESEARCH. 6(11). p.1292-1300
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Abstract
Mouse models have been instrumental in establishing fundamental principles of cancer initiation and progression and continue to be invaluable in the discovery and further development of cancer therapies. Nevertheless, important aspects of human disease are imperfectly approximated in mouse models, notably the involvement of endogenous retroviruses (ERVs). Replication-defective ERVs, present in both humans and mice, may affect tumor development and antitumor immunity through mechanisms not involving infection. Here, we revealed an adverse effect of murine ERVs with restored infectivity on the behavior of mouse cancer models. In contrast to human cancer, where infectious ERVs have never been detected, we found that ERV infectivity was frequently restored in transplantable, as well as genetic, mouse cancer models. Such replication-competent, ERV-derived retroviruses were responsible for unusually high expression of retroviral nucleic acids and proteins in mouse cancers. Infectious ERV-derived retroviruses produced by mouse cancer cells could directly infect tumor-infiltrating host immune cells and fundamentally modified the host's immune defenses to cancer, as well as the outcome of immunotherapy. Therefore, infectious retroviruses, variably arising in mouse cancer models, but not in human cancer, have the potential to confound many immunologic studies and should be considered as a variable, if not altogether avoided. (C) 2018 AACR.
Keywords
IN-VIVO, SPECIES IDENTIFICATION, MELANOMA, CELLS, SITES, MICE

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MLA
Ottina, E., et al. “Restoration of Endogenous Retrovirus Infectivity Impacts Mouse Cancer Models.” CANCER IMMUNOLOGY RESEARCH, vol. 6, no. 11, 2018, pp. 1292–300, doi:10.1158/2326-6066.cir-18-0038.
APA
Ottina, E., Levy, P., Eksmond, U., Merkenschlager, J., Young, G., Roels, J., … Kassiotis, G. (2018). Restoration of endogenous retrovirus infectivity impacts mouse cancer models. CANCER IMMUNOLOGY RESEARCH, 6(11), 1292–1300. https://doi.org/10.1158/2326-6066.cir-18-0038
Chicago author-date
Ottina, E, P Levy, U Eksmond, J Merkenschlager, GR Young, Juliette Roels, JP Stoye, T Tüting, DP Calado, and G Kassiotis. 2018. “Restoration of Endogenous Retrovirus Infectivity Impacts Mouse Cancer Models.” CANCER IMMUNOLOGY RESEARCH 6 (11): 1292–1300. https://doi.org/10.1158/2326-6066.cir-18-0038.
Chicago author-date (all authors)
Ottina, E, P Levy, U Eksmond, J Merkenschlager, GR Young, Juliette Roels, JP Stoye, T Tüting, DP Calado, and G Kassiotis. 2018. “Restoration of Endogenous Retrovirus Infectivity Impacts Mouse Cancer Models.” CANCER IMMUNOLOGY RESEARCH 6 (11): 1292–1300. doi:10.1158/2326-6066.cir-18-0038.
Vancouver
1.
Ottina E, Levy P, Eksmond U, Merkenschlager J, Young G, Roels J, et al. Restoration of endogenous retrovirus infectivity impacts mouse cancer models. CANCER IMMUNOLOGY RESEARCH. 2018;6(11):1292–300.
IEEE
[1]
E. Ottina et al., “Restoration of endogenous retrovirus infectivity impacts mouse cancer models,” CANCER IMMUNOLOGY RESEARCH, vol. 6, no. 11, pp. 1292–1300, 2018.
@article{8670462,
  abstract     = {{Mouse models have been instrumental in establishing fundamental principles of cancer initiation and progression and continue to be invaluable in the discovery and further development of cancer therapies. Nevertheless, important aspects of human disease are imperfectly approximated in mouse models, notably the involvement of endogenous retroviruses (ERVs). Replication-defective ERVs, present in both humans and mice, may affect tumor development and antitumor immunity through mechanisms not involving infection. Here, we revealed an adverse effect of murine ERVs with restored infectivity on the behavior of mouse cancer models. In contrast to human cancer, where infectious ERVs have never been detected, we found that ERV infectivity was frequently restored in transplantable, as well as genetic, mouse cancer models. Such replication-competent, ERV-derived retroviruses were responsible for unusually high expression of retroviral nucleic acids and proteins in mouse cancers. Infectious ERV-derived retroviruses produced by mouse cancer cells could directly infect tumor-infiltrating host immune cells and fundamentally modified the host's immune defenses to cancer, as well as the outcome of immunotherapy. Therefore, infectious retroviruses, variably arising in mouse cancer models, but not in human cancer, have the potential to confound many immunologic studies and should be considered as a variable, if not altogether avoided. (C) 2018 AACR.}},
  author       = {{Ottina, E and Levy, P and Eksmond, U and Merkenschlager, J and Young, GR and Roels, Juliette and Stoye, JP and Tüting, T and Calado, DP and Kassiotis, G}},
  issn         = {{2326-6066}},
  journal      = {{CANCER IMMUNOLOGY RESEARCH}},
  keywords     = {{IN-VIVO,SPECIES IDENTIFICATION,MELANOMA,CELLS,SITES,MICE}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1292--1300}},
  title        = {{Restoration of endogenous retrovirus infectivity impacts mouse cancer models}},
  url          = {{http://dx.doi.org/10.1158/2326-6066.cir-18-0038}},
  volume       = {{6}},
  year         = {{2018}},
}

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