EFFECTS OF SUBTLE CHANGES IN THE SU PROTEIN OF ECOTROPIC MURINE LEUKEMIA-VIRUS ON ITS BRAIN CAPILLARY ENDOTHELIAL-CELL TROPISM AND INTERFERENCE PROPERTIES

PVC-211 murine leukemia virus (MuLV) is a neuropathogenic variant of F riend MuLV (F-MuLV) that causes a rapidly progressive neurodegenerativ e disease in susceptible rodents. PVC-211 MuLV, but not the parental F -MuLV, can infect rat brain capillary endothelial cells (BCEC) efficie ntly, and the major determinant for BCEC tropism of PVC-211 MuLV is lo calized within the Xbal-BamHI fragment of the viral genome containing the 5' half of the env gene. To further dissect the Xbal-BamHI region for its effects on BCEC tropism, we constructed recombinant viruses be tween PVC-211 MuLV and F-MuLV and tested their infectivity on a cell l ine established from rat BCEC. Our results indicated that Glu(116)-to- Gly and Glu(129)-to-Lys substitutions in the background of the F-MuLV envelope SU protein were sufficient for conferring BCEC tropism on the virus. Interference studies of these viruses on Rat-1 fibroblastic ce lls showed that the structure of the SU protein encoded by the Xbal-Ba mHI region also has significant effects on their affinity for the rat ecotropic MuLV receptor. These results support the possibility that st ructural elements I and II of the SU protein are important determinant s for virus-receptor interaction. (C) 1996 Academic Press, Inc.