Novel endogenous type D retroviral particles expressed at high levels in aSCID mouse thymic lymphoma

A xenograft model of the human disease Langerhans cell histiocytosis (LCH) was investigated with severe combined immunodeficiency (SCID) mice. Transpl antation of human LCH biopsy material into SCID mice resulted in the genera tion of mouse tumors resembling lymphomas. A thymoma cell line (ThyE1M6) wa s generated from one of these mice and found to display significant levels of Mg2+-dependent reverse transcriptase activity. Electron microscopy revea led particles with type D retroviral morphology budding from ThyE1M6 cells at a high frequency, whereas control cultures were negative. Reverse transc ription-PCR of virion RNA with degenerate primers for conserved regions of various mouse, human, and primate retroviruses amplified novel sequences re lated to primate type D retroviruses, murine intracisternal A particles, Ja agsiekte sheep retrovirus, and murine long interspersed nuclear elements bu t not other retroviral classes. We demonstrate that these sequences represe nt a novel group of endogenous retroviruses expressed at low levels in mice but expressed at high levels in the ThyE1M6 cell line. Furthermore, we pro pose that the activation of endogenous retroviral elements may be associate d with a high incidence of thymomas in SCID mice.