At least four non-env factors that reside in the LTR, in the 5′-non-coding region, in gag and in part of pol affect neuropathogenicity of PVC-441 murine leukemia virus (MuLV)

PVC-441 murine leukemia virus (MuLV) is neuropathogenic in F344 rats. Recently, an infectious DNA clone was isolated and its nucleotide sequence was determined (J. Virol. 72: 3423–3426. 1998). To identify the viral determinants of neuropathogenicity of the molecularly cloned PVC-441 MuLV, chimeras were constructed between PVC-441 MuLV and F-MuLV clones at appropriate restriction enzyme sites that divide the viral genome approximately in LTR-non-coding, gag-, pol-, and env-gene regions. Results indicated that the LTR-non-coding and the gag-gene regions of PVC-441 MuLV affected independently the neuropathogenicity in combination with the env gene region as evidenced clinically and pathologically. Studies on the distribution of vacuolar degeneration suggested that the pons and cervical spinal cord areas were the primary targets and the large brain was the latest target of PVC-441 MuLV. Further studies with chimeric viruses that were formed in the LTR-non-coding and the gag gene regions revealed that at least four factors affected the neuropathogenicity of PVC-441 MuLV. Two factors were found in the U3, and R-U5-5′-non-coding regions, and at least two factors in the gag gene region that contained the N-terminal part of the pol gene. Among these factors, at least two factors seemed to be ‘cis-acting’ from each other