Resurrection of endogenous retroviruses in antibody-deficient mice
Open accessAbstract
The mammalian host has developed a long-standing symbiotic relationship with a considerable number of microbial species. These include the microbiota on environmental surfaces, such as the respiratory and gastrointestinal tracts, and also endogenous retroviruses (ERVs), comprising a substantial fraction of the mammalian genome. The long-term consequences for the host of interactions with these microbial species can range from mutualism to parasitism and are not always completely understood. The potential effect of one microbial symbiont on another is even less clear. Here we study the control of ERVs in the commonly used C57BL/6 (B6) mouse strain, which lacks endogenous murine leukaemia viruses (MLVs) able to replicate in murine cells. We demonstrate the spontaneous emergence of fully infectious ecotropic MLV in B6 mice with a range of distinct immune deficiencies affecting antibody production. These recombinant retroviruses establish infection of immunodeficient mouse colonies, and ultimately result in retrovirus-induced lymphomas. Notably, ERV activation in immunodeficient mice is prevented in husbandry conditions associated with reduced or absent intestinal microbiota. Our results shed light onto a previously unappreciated role for immunity in the control of ERVs and provide a potential mechanistic link between immune activation by microbial triggers and a range of pathologies associated with ERVs, including cancer.
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Congenital immunodeficiencies affecting antibody production invariably lead to spontaneous establishment of replication-competent pathogenic MLVs as a result of recombination between at least three replication-compromised proviruses.
“Indeed, congenital immunodeficiencies affecting antibody production invariably lead to the spontaneous establishment of replication-competent pathogenic MLVs as a result of recombination between at least three replication-compromised proviruses.”
From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [82]
The paper reports infectious MLVs arising through recombination in antibody-deficient mouse colonies; the recombination passage identifies Emv2, Xmv43 and other endogenous xMLVs, and the tumour passage links the resulting viruses to lymphoma. But it does not support “invariably”: the husbandry passage reports minimal viral expression in some immunodeficient colonies, and the colony-history passage calls emergence unlikely in an individual mouse (all passages labelled Abstract; no page given). The finding is also limited to mice, not congenital immunodeficiencies generally. (LLM, conf=0.89)
Experimental — accuracy not yet measuredRecent studies in mice have demonstrated that the frequency of recombination generating replication-competent retroviruses is increased considerably in certain types of immunodeficiency.
“However, recent studies in mice have demonstrated that this frequency is increased considerably in certain types of immunodeficiency 82,83.”
From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [82]
The paper reports infectious recombinant retroviruses in antibody-deficient mice but not wild-type controls, and describes a high cumulative probability of their emergence in antibody-deficient colonies (Abstract; page unavailable). It does not demonstrate that the frequency of the recombination events themselves increased considerably; emergence and subsequent spread could also account for the difference. (LLM, conf=0.86)
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- Authors
- Young, G. R., Eksmond, U., Salcedo, R., Alexopoulou, L., Stoye, J. P., & Kassiotis, G.
- Affiliations
- National Institute for Medical Research (GB)
- National Institutes of Health (US)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Kassiotis, George
- Venue
- Nature
- Published
- 2012-10-24
- Volume
- 491
- Issue
- 7426
- Pages
- 774-778
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3511586
- OpenAlex
- W2063855257
- Cited by
- 215
- References
- 61
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 11 · 2023: 18 · 2022: 8 · 2021: 13 · 2020: 9 · 2019: 16 · 2018: 15 · 2017: 17 · 2016: 22 · 2015: 18 · 2014: 27 · 2013: 24 · 2012: 2
- FWCI
- 9.93
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- endogenous retroviruses, antibody deficiency, immunodeficient mice, C57BL/6 mice, ecotropic retrovirus, retroviral recombination, gut microbiota
- MeSH terms
- Animals, Animal Husbandry, Antibodies, Viral, Cell Transformation, Viral, Female, Leukemia, Lymphoma, Male, Mice, Inbred C57BL, Leukemia Virus, Murine, Receptors, Antigen, T-Cell, Recombination, Genetic, Viremia, Virus Activation, Immunocompromised Host, Endogenous Retroviruses, Mice
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