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Mouse mammary tumor virus: a virus that exploits the immune system
1Dept. of Microbiology, University of Pennsylvania Medical School, Philadelphia 19104, USA.
Abstract:
Mouse mammary tumor virus (MMTV) causes mammary carcinomas and T-cell tumors in mice. MMTV variants that induce T-cell tumors have a large deletion within the U3 region of the long terminal repeat (LTR) compared to MMTV strains that induce mammary tumors. We provide evidence here that T-cell tropic MMTV strains lack a redundant binding site for a cellular protein called NBP (negative regulatory element binding protein). The lack of NBP-binding sites in T-cell tropic MMTV strains presumably leads to higher levels of transcription in T-cells during the MMTV life cycle and an increased incidence of mutagenic integration events.
Insights
Mouse mammary tumor virus (MMTV) strains that cause T-cell tumors lack a specific binding site for NBP (negative regulatory element binding protein). This absence likely increases MMTV transcription and mutagenic integration in T-cells.
Area of Science:
- Virology
- Oncology
- Immunology
Background:
- Mouse mammary tumor virus (MMTV) is associated with mammary carcinomas and T-cell tumors in mice.
- MMTV strains inducing T-cell tumors exhibit distinct genetic alterations, specifically large deletions in the U3 region of the long terminal repeat (LTR).
Purpose of the Study:
- To investigate the molecular mechanisms underlying the tropism of MMTV variants towards T-cell tumors.
- To identify specific genetic differences in T-cell tropic MMTV strains that contribute to their oncogenic potential.
Main Methods:
- Comparative analysis of MMTV LTR sequences from mammary tumor-inducing and T-cell tumor-inducing strains.
- Investigation of cellular protein binding sites within the MMTV LTR, focusing on NBP (negative regulatory element binding protein).
Main Results:
- T-cell tropic MMTV strains possess a large deletion in the U3 region of the LTR compared to mammary tumor strains.
- Evidence suggests that T-cell tropic MMTV strains lack a critical binding site for the cellular protein NBP.
- The absence of NBP binding sites correlates with higher MMTV transcription levels in T-cells.
Conclusions:
- The lack of NBP binding sites in T-cell tropic MMTV is a key factor in their oncogenicity.
- This molecular alteration likely enhances MMTV transcription and promotes mutagenic integration events within T-cells, leading to tumor development.