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Retrovirus-induced murine motor neuron disease: mapping the determinant of spongiform degeneration within the
Y Paquette1, Z Hanna, P Savard
1Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Canada.
Abstract:
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.
Insights
The Cas-Br-E murine leukemia virus (MuLV) causes paralysis in mice. A specific env gene fragment in Cas-Br-E MuLV is responsible for this neurological degeneration, likely through gp70 binding to a cellular receptor.
Area of Science:
- Virology
- Neuroscience
- Genetics
Background:
- Cas-Br-E murine leukemia virus (MuLV) is known to induce a degenerative myeloencephalopathy.
- This condition in newborn mice leads to hind-limb paralysis, indicating a neurological component.
Purpose of the Study:
- To identify the specific viral DNA sequences within Cas-Br-E MuLV responsible for inducing neurological degeneration.
- To understand the genetic basis of paralysis caused by this specific MuLV strain.
Main Methods:
- Construction of chimeric viruses in vitro using parental genomes from Cas-Br-E MuLV and nonparalytogenic MuLVs.
- Analysis of viral DNA fragments, specifically within the env gene, to determine their role in disease induction.
Main Results:
- A 1.5-kilobase-pair fragment of the Cas-Br-E env gene was found to be sufficient for conferring full paralysis-inducing potential to chimeric viruses.
- A smaller, 372-base-pair fragment within this env region was identified as necessary for full paralysis induction and influenced disease development in a strain-dependent manner.
- This critical domain encodes specific residues of the leader peptide and the N-terminus of gp70.
Conclusions:
- The env gene of Cas-Br-E MuLV contains the determinant for neurological degeneration and paralysis.
- Cas-Br-E MuLV likely induces spongiform degeneration by its gp70 protein binding to a specific cellular receptor.