T cell-mediated immune surveillance suppresses an endogenous retrovirus Emv10 in C57BL/6-Ly5.1 mice

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections that have integrated into host genomes. Although most ERVs are thought to be transcriptionally silent owing to accumulated mutations and epigenetic repression, recent studies have suggested that some ERVs remain biologically active and may influence host immunity and disease. Here, we report that the commonly used congenic mouse strain C57BL/6 (B6)-Ly5.1 harbors an additional endogenous ecotropic murine leukemia virus (eMLV) locus that is absent in wild-type B6 mice. Genomic analyses identified this locus as Emv10, derived from the SJL/J background. Although Emv10 transcripts were barely detectable in immunocompetent mice, B6-Ly5.1 mice exhibited significantly increased CD8⁺ T cell populations compared with wild-type B6 mice, suggesting a constitutive immune response to endogenous viral elements. Notably, in T cell-deficient B6-Ly5.1 mice, Emv10 expression was strongly induced in B cells, and viral RNA was detected in culture supernatants. Moreover, these mice spontaneously developed aggressive B cell lymphomas with markedly elevated eMLV expression. These findings demonstrate that T cell-mediated immune surveillance continuously suppresses ERV-expressing cells and prevents ERV-associated lymphomagenesis. Our study identifies a previously unrecognized genetic and functional distinction between B6 and B6-Ly5.1 mice and underscores the importance of considering endogenous retroviral backgrounds in immunological studies.