Ecotropic virus in mice that are modifiers of autoimmunity

The fairly recent realization that endogenous elements play an important role in the immune system has revived a great interest in them. We now know that endogenous retroelements are adjuvants in the immune response to T cell-independent type 2 antigens; and retroelements are implicated in monogenic and polygenic (“spontaneous”) autoimmune disease.

In C57BL/6 mice, de novo recombinant ecotropic virus is held in check by the adaptive immune system; in its absence, lymphomas are generated. Long time ago, endogenous murine leukemia virus has also been suggested to contribute to both autoimmune disease and lymphoma in the NZB mouse and in the (NZB x NZW) F1 (abbreviated B/W) mouse. However, it turned out that the NZB and NZW mice produce xenotropic virus only (although an ecotropic virus can be induced in NZW). This made it difficult to explain lymphoma formation late in life of the NZB mouse, and somewhat earlier in the B/W mouse: In general, mouse lymphomas are caused by insertional mutagenesis, which requires infectious virus.

With the beginning of the AIDS epidemy in the 1980s, mouse retrovirology has been overshadowed by HIV research, and publications on retroelements in immunology have been few and far between. As a result, many pieces of information are missing. In a recent paper, we have catalogued the endogenous retroviruses present in the plasma of NZB, NZW and B/W mice by sequencing, and we provide evidence for pseudotyping of xenotropic retrovirus in NZB mice. This is important, when one considers the causes of lymphomagenesis in old mice. We also show de novo retroviral insertions in hyperproliferating splenocytes, peritoneal B cells and lymphoma in aging B/W mice. These insertions are in or near putative oncogenes and tumor suppressor genes. Finally, we isolated and determined the complete sequence of an ecotropic NZW virus, which caused a de novo integration in a B/W lymphoma.

Check out the paper at J Gen Virol. 2015, 96:3396-410.