Moloney Murine Leukemia Virus Temperature-Sensitive Mutants: A Model for Retrovirus-Induced Neurologic Disorders

Abstract

In the early 1960s Stansly observed in BALB/c mice a neurogenic paralysis of the hind limb associated with the cell-free transmission of a reticulum cell sarcoma, and suggested that the paralytogenic agent and the neoplastic virus could be the same (Stansly 1965). About a decade later, the discovery by Gardner and coworkers (1973) that an isolate of murine leukemia virus (MuLV) of wild mouse origin not only possesses the ability to cause lymphomas but also the ability to induce a nononcogenic, yet fatal disease of the CNS further suggested that MuLV is not only lymphomagenic but also neurovirulent. This naturally occurring MuLV-induced neurologic disorder was later found to be readily and reproducibly transmitted to susceptible laboratory mice (Officer et al. 1973; Oldstone et al. 1977), establishing the fact that this MuLV-related neurologic disease not only occurs in wild mice but can also be induced in laboratory mice (for review see Gardner 1985). Since then at least three instances of neurologic disorders induced by MuLV in laboratory mice and rats have been reported. In two of these instances, temperature-sensitive (ts) mutants of Moloney murine leukemia virus (MoMuLV) were involved. In the first case a group of ts mutants of MoMuLV-TB, a variant of MoMuLV, was found to be able to induce a rapidly progressive paralytic disease in mice (McCarter et al. 1977; Wong et al. 1983). The second case, which was reported by Billello and coworkers (1986), also involved a ts mutant of MoMuLV designated ts Mo BA-I MuLV, which was initially obtained from Peter Nobis of the University of Hamburg, Federal Republic of Germany.