VIRAL DETERMINANTS THAT CONTROL THE NEUROPATHOGENICITY OF PVC-211 MURINE LEUKEMIA-VIRUS IN-VIVO DETERMINE BRAIN CAPILLARY ENDOTHELIAL-CELL TROPISM OF THE VIRUS IN-VITRO
M. Masuda et al., VIRAL DETERMINANTS THAT CONTROL THE NEUROPATHOGENICITY OF PVC-211 MURINE LEUKEMIA-VIRUS IN-VIVO DETERMINE BRAIN CAPILLARY ENDOTHELIAL-CELL TROPISM OF THE VIRUS IN-VITRO, Journal of virology, 67(8), 1993, pp. 4580-4587
PVC-211 murine leukemia virus (MuLV) is a neuropathogenic, weakly leuk
emogenic variant of the nonneuropathogenic, highly leukemogenic Friend
MuLV (F-MuLV). Chimeric viruses constructed from PVC-211 MuLV clone 3
d and F-MuLV clone 57 indicate that the env gene of PVC-211 MuLV conta
ins the determinant(s) responsible for pathological changes in the cen
tral nervous system. However, sequences within the 5' one-third (AatII
-EcoRI region) of the PVC-211 MuLV genome, which include the 5' leader
sequence, the gag gene, and the 5' quarter of the pol gene, are also
needed in conjunction with the env gene determinant(s) to cause clinic
ally evident neurological disease in the majority of virus-infected an
imals after a short latency. in the presence of the AatII-EcoRI region
of the PVC-211 MuLV genome, the PVC-211 MuLV env gene sequences encod
ing the amino-terminal half of the SU protein, which contains the rece
ptor-binding region of the protein, were sufficient to cause rapidly p
rogressive neurological disease. When PVC-211 MuLV, F-MuLV, and variou
s chimeric viruses were tested for their ability to replicate in cultu
red brain capillary endothelial cells (BCEC), the primary site of PVC-
211 MuLV replication within the central nervous system, there was a di
rect correlation between the replication efficiency of a virus in BCEC
in vitro and its ability to cause neurological disease in vivo. This
observation indicates that the sequences in PVC-211 MuLV that render i
t neuropathogenic affect its replication in BCEC and suggests that rap
id and efficient replication of the vims in BCEC is crucial for the pa
thological changes in the central nervous system that result in develo
pment of neurological disease.