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Biologic and molecular characterization of two newly isolated ras-containing murine leukemia viruses
Abstract:
A murine sarcoma virus (MSV) was recovered from an (NFS X NS.C58v-1) F1 mouse which developed splenic sarcoma and erythroleukemia 6 months after inoculation with a mink cell focus-inducing murine leukemia virus (MuLV) isolated from an NFS mouse infected with a wild mouse ecotropic MuLV. The MSV, designated NS.C58 MSV-1, induced foci of transformation in mouse and rat fibroblasts, and inoculation of mice of various strains 2 weeks of age or younger resulted in erythroleukemia and sarcomatous lesions in spleen, lymph node, and brain. The MSV provirus was molecularly cloned from a genomic library prepared from transformed non-producer rat cells. The 8.8-kilobase proviral DNA contained a 1.0-kilobase p21 ras coding segment which replaced most of the gp70-encoding portion of an MuLV, most likely the endogenous C58v-1 ecotropic virus. The ras oncogene is closely related to v-Ha-ras by hybridization, expression of p21 protein, and nucleotide sequence. It is nearly identical in sequence to v-bas, the only previously described transduced, activated mouse c-ras. At position 12 in the p21 coding region, arginine is substituted for the naturally occurring glycine present in c-ras. A second MSV isolate is described which is similar to NS.C58 MSV-1 except for a 100- to 200-base-pair deletion in the noncoding region of the ras-containing insert.
Insights
Researchers identified a novel murine sarcoma virus (MSV) that causes erythroleukemia and sarcomas in mice. This MSV contains a ras oncogene, similar to known oncogenes, and shows potential for cancer research.
Area of Science:
- Virology
- Oncology
- Molecular Biology
Background:
- Murine sarcoma viruses (MSV) are known to induce tumors in rodents.
- Murine leukemia viruses (MuLV) can contribute to the development of MSV.
- Oncogenes, such as ras, play a critical role in cellular transformation and cancer development.
Purpose of the Study:
- To characterize a newly isolated MSV, designated NS.C58 MSV-1.
- To investigate the oncogenic potential and genetic makeup of this MSV.
- To understand the role of the ras oncogene in MSV-induced malignancies.
Main Methods:
- Isolation and characterization of MSV from infected mice.
- Induction of transformation in fibroblast cell lines.
- Molecular cloning and sequencing of the MSV provirus.
- Analysis of the ras oncogene sequence and its relation to other ras genes.
Main Results:
- A novel MSV (NS.C58 MSV-1) was recovered from mice with splenic sarcoma and erythroleukemia.
- This MSV induced sarcomatous lesions and erythroleukemia in young mice.
- The MSV provirus contained a ras oncogene, replacing a portion of the MuLV genome.
- The ras oncogene showed high similarity to v-Ha-ras and v-bas, with a specific glycine-to-arginine substitution at position 12.
Conclusions:
- NS.C58 MSV-1 is a potent oncogenic virus capable of inducing diverse neoplastic conditions.
- The presence and specific mutation within the ras oncogene are key determinants of its transforming ability.
- This MSV isolate provides a valuable model for studying ras-mediated oncogenesis and viral-induced cancers.