Determination of virulence properties of leukemia viruses.

Understanding the basis of virulence of leukemia viruses is a major unsolved problem. Under natural and experimental conditions, retroviruses may replicate freely in the host with no profound consequence. Such is typically the case for vertically transmitted viruses that express early in life, e.g., the endogeneous baboon and murine Akv Grus [I]. We call such viruses avirulent. Horizontally transmitted retroviruses usually induce disease, but typically only after a lengthy latent period and then in only a small fraction of infected individual~ [2]. Viruses of moderate virulence include feline, bovine, and gibbon ape leukemia viruses. In these cases, rampant viremia is usually followed by immune suppression of the infection. Onset of frank leukemia is delayed by months or years and is a low probability event. The virusassociated with adult T-cell lymphoma in humans, HTLV, probably falls into this class of virus (Gallo et al., this volume). Some experimentally manipulated leukemia viruses are highly virulent. For example, the Moloney strain of murine leukemia virus induces a rapid (3 months to death) disease in a high proportion of injected animals. To approach the problem of a murine leukemia virus, we selected avirulent and highly virulent strains for intensive study. Our initial goal was to isolate strains of murine leukemia virus that were isogenic except for the virulence phenotype. This cri-