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 Friend MuLV (F-MuLV) that causes a rapidly progressive neurodegenerative disease in susceptible rodents. PVC-211 MuLV, but not the parental F-MuLV, can infect rat brain capillary endothelial cells (BCEC) efficiently, and the major determinant for BCEC tropism of PVC-211 MuLV is localized within the XbaI-BamHI fragment of the viral genome containing the 5' half of the env gene. To further dissect the XbaI-BamHI region for its effects on BCEC tropism, we constructed recombinant viruses between PVC-211 MuLV and F-MuLV and tested their infectivity on a cell line established from rat BCEC. Our results indicated that Glu116-to-Gly and Glu129-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 cells showed that the structure of the SU protein encoded by the XbaI-BamHI region also has significant effects on their affinity for the rat ecotropic MuLV receptor. These results support the possibility that structural elements I and II of the SU protein are important determinants for virus-receptor interaction.
Masuda
M
M
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland 21702, USA.
Hanson
C A
CA
Alvord
W G
WG
Hoffman
P M
PM
Ruscetti
S K
SK
Masuda
M
M
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000821:virology*; D002460:Cell Line; D004279:DNA, Viral; D004730:Endothelium, Vascular / Q000821:virology*; D005347:Fibroblasts / Q000166:cytology; D005622:Friend murine leukemia virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005822:Genetic Vectors; D051379:Mice; D008969:Molecular Sequence Data; D011533:Proviruses / Q000235:genetics; D051381:Rats; D011991:Receptors, Virus / Q000378:metabolism; D011995:Recombination, Genetic; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014762:Viral Interference; D016662:Virus Integration
D004279:DNA, Viral; D011991:Receptors, Virus; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins