The major goal of this project is a basic understanding of the biological and biochemical basis of Fv-1 restriction, a naturally-occurring cellular system which inhibits the replication of specific N- or B-tropic murine leukemia viruses. The studies involve a variety of cell culture techniques for quantitating virus replication, the inactivation of viruses by gamma radiation or by heating, and the detection of viral proteins by radioimmunoassay. Infection of a Balb/3T3 mouse cell (Fv-1b) with a single N-tropic leukemia virus particle results in the temporary abrogation of cellular Fv-1 restriction. Abrogation appears to be accompanied by the early appearance of viral p30 determinants and may represent an entirely new viral metabolic pathway. Some N-type cells appear to display other restriction systems in addition to Fv-1. A new method for the detection and quantitation of defective murine leukemia viruses has been developed and is being used to study a group of recently isolated viral mutants.