MOLECULAR BASIS FOR THE ACUTE ERYTHROLEUKEMIAS INDUCED BY MURINE RETROVIRUSES

脾灶形成病毒（SFFV）的Friend株引起

The Friend strain of the spleen focus forming virus (SFFV) causes an acute erythroleukemia in mice. Studies have been aimed at defining the area(s) of the viral genome responsible for pathogenicity and erythroid cell specificity and determining the mechanism by which SFFV alters erythroid cell growth and differentiation. Using a Moloney MuLV-based retroviral vector, we have demonstrated that the SFFV env gene, when introduced into mice in the absence of other SFFV genes, is pathogenic. The disease induced is indistinguishabled from that induced by the entire SFFV genome, proving that the primary effect of the virus, which is to alter the requirements of erythroid cells for erythropoietin (Epo), is due solely to the product of its env gene. To further understand how the viral env gene product alters erythroid cells, we have continued our studies of variants of the virus, designated SFFVp and SFFVA, both of which induce acute erythroleukemia but differ in their effects on erythroid cells as well as in the processing of their env gene products. We were previously able to localize the biological and biochemical differences between the two viruses to a 678 bp region in the 3' half of the env gene. We have now further localized the critical region to a 120 bp fragment from the of the protein. Finally, we have attempted to understand how the SFFV envelope glycoprotein alters the requirements of erythroid cells for Epo by comparing normal and virus-infected cells for Epo receptors. Our results indicate that spleen cells from SFFVp-infected mice, which proliferate and differentiate in the apparent absence of Epo, have the same number of Epo receptors as normal erythroid cells, whereas spleen cells from SFFVA-infected mice, which proliferate better in the presence of Epo and which require Epo for differentiation, have 4 times as many Epo receptors. Cross-linking studies show no obvious quantitative differences in the receptors on normal and SFFV-infected cells.