The experiments in this proposal are designed to study the significance of the association of the accumulation of unintegrated viral DNA with retroviral infections that cause cell dysfunction or death. Two model systems will be used for these studies: (1) avian leukosis virus-induced osteopetrosis; an infection in which the accumulation of unintegrated viral DNA is associated with cell dysfunction and (2) AIDS-virus infected T- cells; an infection in which the accumulation of unintegrated viral DNA occurs in cells undergoing cytopathic effects. The proposed experiments will characterize and quantitate viral and proviral DNA synthesis, the expression of viral mRNAs and the expression of viral envelope glycoproteins in cells undergoing the accumulation of unintegrated viral DNA. The proposed experiments also test the hypothesis that the accumulation of unintegrated viral DNA in different retrovirus-induced diseases is associated with a common phenomenon, the failure of the infection to establish envelope glycoprotein-mediated superinfection resistance.
