The main goal of this project is to define different retrovirus-induced pathogenic mechanisms both at the cellular level in intact animals and at the molecular or biochemical level. Retrovirus-induced hemolytic anemia has been found to be an important early pathogenic effect after inoculation of newborn mice with Friend murine leukemia helper virus (F-MuLV). This effect was previously undetected because the main clinical signs of anemia and splenomegaly were identical both in the early hemolytic phase and in the late erythroleukemia phase of the disease. These stages were distinguished in the present work by reticulocyte counts showing high levels during hemolysis and low levels during leukemia. Two closely related F-MuLV strains have been found to differ in their ability to induce both of these pathogenic effects, the lower virulence strain inducing only mild hemolysis and having a very prolonged latency of induction of leukemia. Molecular cloning of this low virulence virus strain has been done in our laboratory and recombinant retroviruses were constructed using the low and high virulence strains. The results indicated that the severity of the early and late pathogenic effects could be dissociated in certain recombinant viruses. This suggested that different portions of the viral genome were responsible for each of these phases of the disease.
