UNIQUE SEQUENCE AND LESIONAL TROPISM OF A NEW VARIANT OF NEUROPATHOGENIC FRIEND MURINE LEUKEMIA-VIRUS

FrC6 murine leukemia virus (MuLV) is a replication-competent, neuropat hogenic Variant derived from Friend MuLV (F-MULV) complex The A8 virus (a molecular clone of the FrC6 virus) induced marked spongiform degen eration in the brain similar to the FrC6 virus, but only mild lesions were found in the spinal cord. in contrast, PVC211 virus, which is als o a neuropathogenic F-MuLV variant, caused marked spongiform degenerat ion in the spinal cord. Virus recovery from the spinal cord of A8 viru s-infected rat was the same as that of PVC211-infected rat, indicating that there is no direct correlation between the titer of virus and th e intensity of lesions. Furthermore, rats infected with the A8 virus a t 3 weeks of age did not undergo spongiform degeneration, although rec overy of high titer of virus occurred in the central nervous system (C NS]. Studies using chimeric viruses between the A8 virus and nonneurop athogenic F-MuLV clone 57 also indicated that the sequences responsibl e for Virus titers in the CNS and neuropathogenicity are different. Th e chimeric Virus studies proved that the env gene and the LTR and/or 5 ' leader sequence of A8 are critical for the induction of neuropathoge nicity. These sequences in A8 and PVC211 were compared, focusing in on the sites that account for neurovirulence and Viral lesional tropism. (C) 1997 Academic Press.