Retrovirus-induced murine motor neuron disease: mapping the determinant of spongiform degeneration within the envelope gene.
The Cas-Br-E murine leukemia virus (MuLV) induces a degenerative myeloencephalopathy leading to hind-limb paralysis when inoculated into newborn mice. To map the viral DNA sequences encoding the determinant of neurological degeneration, we constructed chimeric viruses in vitro with parental genomes from Cas-Br-E MuLV and from nonparalytogenic MuLVs. We found that a 1.5-kilobase-pair env Cas-Br-E fragment was sufficient to confer the full paralysis-inducing potential to chimeric viruses. This region encodes the 19 carboxyl-terminal residues of the leader sequence, all of gp70, and the 45 amino-terminal residues of the transmembrane protein (p15E). Within this env region, we identified a 372-base-pair fragment which was necessary for the full paralysis-inducing potential of the virus and which influenced the development of the disease in a strain-dependent manner. This domain encodes the 19 carboxyl-terminal residues of the leader peptide and the first 67 amino-terminal residues of gp70. We propose that Cas-Br-E MuLV induces spongiform degeneration through binding of its gp70 to a specific cellular receptor.
Paquette
Y
Y
Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Canada.
Hanna
Z
Z
Savard
P
P
Brousseau
R
R
Robitaille
Y
Y
Jolicoeur
P
P
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology; D002874:Chromosome Mapping; D004274:DNA, Recombinant; D005814:Genes, Viral; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000472:pathogenicity*; D051379:Mice; D009410:Nerve Degeneration; D010243:Paralysis / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D012191:Retroviridae Proteins / Q000235:genetics*; D013116:Spinal Cord / Q000473:pathology; D014759:Viral Envelope Proteins / Q000235:genetics*
D004274:DNA, Recombinant; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins