Related Experiment Videos
Long terminal repeat sequences impart hematopoietic transformation properties to the myeloproliferative sarcoma virus
Abstract:
The myeloproliferative sarcoma virus not only transforms fibroblasts but also causes extensive expansion of the hematopoietic stem cell compartment on infection of adult mice. Similar to the Moloney sarcoma virus, it carries the mos oncogene. Moloney sarcoma virus, however, does not induce myeloproliferation and leukemia in adult mice. The difference between the two viruses was explored by using their molecularly cloned genomes and the cellular mos oncogene to construct recombinant genomes. It was shown that the U3 region of the viral long terminal repeat (LTR) has a decisive function in determining the target cell specificity of the myeloproliferative sarcoma virus. Any mos gene, whether of cellular or viral origin, is sufficient in conjunction with the proper LTR to induce myeloproliferation. Our results indicate that the pathogenicity of acutely transforming viruses is determined not only by the oncogene but also by sequences in the viral LTR.
Insights
The myeloproliferative sarcoma virus (MPSV) causes hematopoietic stem cell expansion due to its U3 region in the long terminal repeat (LTR), not just the mos oncogene. This LTR sequence dictates target cell specificity and pathogenicity.
Area of Science:
- Virology
- Oncology
- Molecular Biology
Background:
- Myeloproliferative sarcoma virus (MPSV) transforms fibroblasts and expands hematopoietic stem cells in mice.
- Both MPSV and Moloney sarcoma virus (MSV) carry the mos oncogene, but only MPSV induces myeloproliferation and leukemia in adult mice.
Purpose of the Study:
- To investigate the molecular basis for the differing pathogenicity of MPSV and MSV.
- To determine the role of the mos oncogene and viral regulatory sequences in MPSV-induced myeloproliferation.
Main Methods:
- Construction of recombinant viral genomes using molecularly cloned MPSV and MSV genomes.
- Inclusion of the cellular mos oncogene in recombinant genome construction.
- Infection of adult mice with recombinant viruses to assess pathogenicity and target cell specificity.
Main Results:
- The U3 region of the viral long terminal repeat (LTR) of MPSV was identified as the critical determinant of target cell specificity.
- The mos oncogene, whether of viral or cellular origin, was sufficient to induce myeloproliferation when combined with the appropriate LTR.
- Viral LTR sequences play a crucial role in determining the pathogenicity of acutely transforming viruses.
Conclusions:
- Pathogenicity of acutely transforming viruses is influenced by both the oncogene and sequences within the viral LTR.
- The U3 region of the LTR is a key factor in MPSV's ability to induce myeloproliferation and target hematopoietic stem cells.