Genetics of expression of xenotropic virus and autoimmunity in NZB mice

Abstract

CERTAIN retroviruses (RNA tumour viruses) have been implicated in the autoimmune disease of New Zealand mice¹. These mice produce large numbers of xenotropic retroviruses^2,3 and contain high concentrations of the retroviral envelope antigen gp 69/71 in their serum and tissues⁴. Moreover, gp 69/71 and the corresponding antibodies contribute to the immune deposits in the nephritic kidneys of NZB and (NZB × NZW)F₁ mice⁴. Nevertheless, it is not established that xenotropic viruses are the primary cause of the autoimmune disease of NZB mice. Conceivably, these agents may be involved only secondarily. The presence of RNA viruses in NZB mice may explain neither the production of antibodies against DNA, nucleoproteins, and erythrocyte antigens nor the anomalies of T- and B-lymphocyte function⁵. Transmission of autoimmunity has not been achieved with cell-free filtrates from NZB mice⁶, nor by transplanting NZB lymphomas⁷ which are known to produce large numbers of virus particles⁸. Only spleen cells from old NZB mice can transmit the autoimmune disorder⁶. Transmission of the disease with cell-free extracts is unlikely to succeed because the NZB xenotropic virus cannot productively infect mouse cells; it can infect only cells of heterologous species^2,3. Here we deal with the vertical transmission of NZB viral genes as Mendelian traits—a phenomenon that has been demonstrated with other retroviruses⁹—to test the hypothesis that the development of autoimmunity in NZB mice and their crosses is independent of the expression of high titres of xenotropic viruses. We have found that the high grade expression of infectious xenotropic virus characteristic of NZB mice is a genetically determined trait. Two independently segregating loci seem to specify the NZB phenotype. So far, animals that are virologically like NZB have failed to develop signs of autoimmune disease.