Mouse mammary tumor virus

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Mouse mammary tumor virus
Systematics
Classification : Viruses
Area : Riboviria
Empire : Pararnavirae
Phylum : Artverviricota
Class : Revtraviricetes
Order : Ortervirales
Family : Retroviridae
Subfamily : Orthoretrovirinae
Genre : Beta retro virus
Type : Mouse mammary tumor virus
Taxonomic characteristics
Genome : (+) ssRNA , linear
Baltimore : Group 6
Cover : available
Scientific name
Mouse mammary tumor virus
Short name
MMTV
Left
NCBI  Taxonomy: 11757
NCBI  Reference: AF033807
ICTV Taxon History: 201854995
ICTVdB Virus Code : 00.061.1.01.001

The mouse mammary tumor virus (MMTV) (engl. Mouse mammary tumor virus ) is a retrovirus , that, in certain mouse strains tumors of the mammary glands can trigger (breast tumors).

Discovery of MMTV - the "breast milk factor"

The virus was first described in 1936 by John Joseph Bittner at the Roscoe B. Jackson Memorial Laboratory in Bar Harbor , Maine . In the previous years, repeated inbreeding had produced laboratory mouse strains with a very high incidence of mammary tumors, particularly the C3H mouse line. It was noticeable that the predisposition to develop breast tumors was practically exclusively transmitted through the maternal line. When a female mouse from a “healthy” laboratory mouse strain (without accumulated breast tumors) was crossed with a male C3H mouse, the offspring had hardly any breast tumors, while in the opposite case (female C3H mouse, male “healthy” mouse) almost 100% of the offspring developed mammary tumors.
The main takeaway from Bittner and coworkers was that they discovered that the reason for this was a factor in breast milk . If the offspring were not fed from the mother's milk of C3H mice, they remained healthy. Apparently, a disease-causing agent was passed on through breast milk. This agent was initially referred to as " the milk influence " or " the milk factor " because it was initially not clear what it was exactly. The virus was first described using an electron microscope at the end of the 1940s . The complete nucleotide sequence was not revealed until the 1980s .

Taxonomy

Taxonomically, the MMTV belongs to the retrovirus family and to the beta retrovirus genus.

Disease picture and molecular biology

MMTV causes tumors of the mammary gland in certain strains of mice. These tumors can grow to be significant. However, they do not show the tendency to metastasize . Therefore, the term " breast cancer " is not really appropriate. Histologically, too , the tumors resemble a mammary gland hyperplasia rather than a carcinoma . Occasionally, MMTV can also lead to T-cell lymphoma in infected mice. MMTV promotes the development of tumors by integrating itself into the vicinity of oncogenes in the mouse genome (“insertion mutagenesis”). As a result, these oncogenes come under the control of control sequences of the virus in the area of ​​so-called long terminal repeats (LTR) and are permanently activated in an uncontrolled manner. MMTV also has a special gene ( sag ) that acts as a superantigen and indirectly promotes the multiplication of virus-infected cells. Also of interest is the fact that the activity of the long terminal repeats is strongly influenced by sex hormones and other steroids .

MMTV can only spread if a certain bacterial flora is present. MMTV requires special bacterial lipopolysaccharides in order to be bound by the toll-like receptor 4 (TLR-4) and taken up into the cell. MMTV is thus the first retrovirus that has been shown to require special bacteria for infection.

Importance for research

As mentioned above, the MMTV-induced mouse mammary tumors are only suitable to a limited extent as animal models for human breast cancer . The MMTV long terminal repeats can be used to “switch on” certain genes in mouse mammary gland cells, e.g. B. in recombinant retroviruses or transgenic mice, which are used as animal models in breast cancer research.

Several research groups reported traces of a possible breast cancer virus from preparations made by human breast cancer patients. However, the significance of these findings is controversial. Involvement of the mouse mammary tumor virus MMTV in human breast cancer seems unlikely due to the available data, although MMTV in human cell culture very efficient human mammary gland - epithelial cells to infect.

See also

Web links

Literature and Sources

  1. ↑ a b c d e ICTV: ICTV Taxonomy history: Commelina yellow mottle virus , EC 51, Berlin, Germany, July 2019; Email ratification March 2020 (MSL # 35)
  2. ^ JJ Bittner: Some possible effects of nursing on the mammary tumor incidence in mice. In: Science. 84, 1936, pp. 162-169. PMID 17793252
  3. ^ JJ Bittner: The milk influence of breast tumor in mice. In: Science. 95, 1942, pp. 462-463. PMID 17736889
  4. ↑ ICTV database
  5. ↑ M. Kane, LK Case et al .: Successful Transmission of a Retrovirus Depends on the Commensal Microbiota. In: Science. 334, 2011, pp. 245-249, doi: 10.1126 / science.1210718 .
  6. ↑ A. Bindra, p Muradrasoli, R. Kisekka, H. Nordgren, F. warning Berg, J. Blomberg: Search for DNA of exogenous mouse mammary tumor virus-related virus in human breast cancer samples. In: J Gen Virol. 88, 2007, pp. 1806-1809. PMID 17485542 .
  7. ^ O. Frank, C. Verbeke, N. Schwarz, J. Mayer, A. Fabarius, R. Hehlmann, C. Leib-Mösch, W. Seifarth: Variable transcriptional activity of endogenous retroviruses in human breast cancer. In: J Virol. 82 (4), 2008, pp. 1808-1818. PMID 18077721
  8. ↑ S. Indic, WH Günzburg, P. Kulich, B. Salmons, F. Rouault: Rapid spread of mouse mammary tumor virus in cultured human breast cells. In: Retrovirology. 4, 2007, p. 73 (full text)