ROLE OF ENDOGENOUS AND RECOMBINANT RETROVIRUSES IN LEUKEMIA AND DIFFERENTIATION

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The main objective of this project is study of mechanisms of retrovirus-induced pathogenesis. We have been studying anemia and erythroleukemia induced by neonatal inoculation of mice with Friend murine leukemia helper virus (F-MuLV). This disease has two separate pathogenic phases both resulting in anemia and splenomegaly. In the first phase virus infection of erythroid precursors causes premature destruction of erythrocytes, giving a hemolytic anemia; splenomegaly results from compensatory erythropoiesis. The second phase consists of erythroleukemia with splenomegaly and anemia due to lack of production and differentiation of erythrocytes. Using two virus variants differing in virulence it was shown that the viral envelope gene was primarily responsible for the induction of early severe hemolytic anemia, whereas the viral LTR region had the main influence on latency of infection of erythroleukemia. Current efforts are aimed at determining the precise gene sequences responsible for each of these effects.