Mouse mammary tumor virus
Mouse mammary tumor virus | |
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Virus classification | |
(unranked): | Virus |
Realm: | Riboviria |
Kingdom: | Pararnavirae |
Phylum: | Artverviricota |
Class: | Revtraviricetes |
Order: | Ortervirales |
Family: | Retroviridae |
Genus: | Betaretrovirus |
Species: | Mouse mammary tumor virus
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Mouse mammary tumor virus (MMTV) is a milk-transmitted
Infection and life cycle
Several mouse strains carry the virus endogenously, but it is also
The mouse mammary tumor virus (MMTV) has formerly been classified as a simple
MMTV codes for the retroviral structural genes and additionally for a
As a retrovirus the MMTV is able to insert its viral genome in the host genome. The virus RNA genome is reverse transcribed by reverse transcriptase into DNA. This DNA intermediate state of the virus is called the provirus. When the virus DNA is inserted inside or even near a gene, it is able to change the expression of that gene and potentially produce an oncogene which might eventually develop into cancer.[7] The viral genome is able to cause cancer only if it alters the expression of an oncogene. If the viral genome is inserted in a "silent" region of the host genome then it is harmless or may cause other diseases. High levels of MMTV are expressed in lymphoid leukemias of mouse strain GR and DBA/2 which contain extra integrated MMTV proviruses. These leukemias are active when cells are transferred to other mice.[8]
When the virus genome is inserted inside the host genome it is then able to transcribe its own viral genes. In F. U. Reuss and J. M. Coffin (2000) experiments it is mentioned that the expression of the virus genome is activated by an enhancer element that is present in the U3 region of the long terminal repeat of the genome.[9] In addition the expression of the genome is activated specifically in the mammary gland cells.[9] Estrogen is able to further activate the expression of the viral genome.[7] The expression of sag gene which is present in the provirus is responsible for the production of a superantigen.[6]
MMTV can be transferred either through an exogenous or endogenous route. If the virus is transferred exogenously, it is passed from the mother mouse to her pups through her milk.[10]
Alternatively, pups can be infected vertically through endogenous infection, inheriting the virus directly from their mother in the germline. Mice that become infected in this way have higher rates of occurrence of tumors. A retrovirus is endogenous to its host once the proviral DNA is inserted into the chromosomal DNA. As a result, mice with endogenous MMTV have the virus's DNA in every cell of its body, as the virus is present in the DNA of the sperm or egg cell from which the animal is conceived.[citation needed]
Hormonal responsiveness of integrated MMTV DNA
Endogenous MMTV reacts to the whole range of
When the mouse reaches puberty the virus begins to express its messenger RNA in the estrogen sensitive tissues. As a result, after puberty all mammary cells will contain the active retrovirus and begin to replicate in the genome and express viral messenger RNA in all new mammary tissue cells.[10]
The MMTV promoter in models of human breast cancer
The LTR (
The MMTV promoter is used in the PyMT model system of
Notes
- S2CID 31163817.
- TIME magazine. 18 March 1946. Archived from the originalon February 19, 2011.
- PMID 16282474.
- PMID 15914215.
- PMID 9621071.
MMTV encodes a superantigen (Sag) that, when expressed on the surface of B cells or other antigen-presenting cells, activates a large number of T cells by interaction with specific T-cell receptor β chains. The resulting T-cell response in turn stimulates the infected B cells to proliferate and thus amplifies the number of virus-infected cells and potential target bystander cells
- ^ S2CID 26055839.
However, the ultimate targets of MMTV are mammary gland cells, which begin dividing during puberty...The infected lymphoid cells then bring virus to the cells of the developing mammary gland, thereby also allowing the virus to overcome its spatial problem... SAg activity is required for efficient viral infection of the mammary epithelial cells and consequent tumorigenesis...Thus, SAg-mediated stimulation of lymphoid cells is needed for their infection and for virus spread between mammary gland cells
- ^ S2CID 4316435.
- PMID 6292463.
- ^ PMID 10933730.
- ^ PMID 14972564.
- PMID 2838812.
- S2CID 40515926.
- PMID 23520493.
- PMID 10713687.
References
- Bhadra, Sanchita; Lozano, Mary M.; Payne, Shelley M.; Dudley, Jaquelin P. (1 January 2006). "Endogenous MMTV Proviruses Induce Susceptibility to Both Viral and Bacterial Pathogens". PLOS Pathogens. 2 (12): e128. PMID 17140288.
- Cammack, Richard; Smith, Anthony Donald; Attwood, Teresa K.; et al. (eds.). "Bittner factor or Bittner particle former name for murine mammary tumour virus". Oxford Dictionary of Biochemistry and Molecular Biolog. p. 79.
- Courreges, M. C.; Burzyn, D.; Nepomnaschy, I.; Piazzon, I.; Ross, S. R. (31 January 2007). "Critical Role of Dendritic Cells in Mouse Mammary Tumor Virus In Vivo Infection". Journal of Virology. 81 (8): 3769–77. PMID 17267484.
- Fernandez-Cobo, Mariana; Melana, Stella M; Holland, James F; Pogo, Beatriz GT (1 January 2006). "Transcription profile of a human breast cancer cell line expressing MMTV-like sequences". Infectious Agents and Cancer. 1 (1): 7. PMID 17173685.
- Indik, S. (1 August 2005). "Mouse Mammary Tumor Virus Infects Human Cells". Cancer Research. 65 (15): 6651–9. PMID 16061645.
- Indik, Stanislav; Günzburg, Walter H; Kulich, Pavel; Salmons, Brian; Rouault, Francoise (1 January 2007). "Rapid spread of mouse mammary tumor virus in cultured human breast cells". Retrovirology. 4 (1): 73. PMID 17931409.
- Lawson, JS; Günzburg, WH; Whitaker, NJ (June 2006). "Viruses and human breast cancer". Future Microbiology. 1 (1): 33–51. PMID 17661684.
- Levine, Paul H.; Pogo, Beatriz G.-T.; Klouj, Afifa; Coronel, Stephanie; Woodson, Karen; Melana, Stella M.; Mourali, Nejib; Holland, James F. (15 August 2004). "Increasing evidence for a human breast carcinoma virus with geographic differences". Cancer. 101 (4): 721–6. S2CID 42247400.
- Salmons, B; Lawson, JS; Gunzburg, WH (December 2014). "Recent developments linking retroviruses to human breast cancer: infectious agent, enemy within or both?". Journal of General Virology. 95 (12): 2589–93. PMID 25217613.