Retrovirus-host interactions. The mouse mammary tumor virus model
1Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Switzerland.
Abstract:
Mouse mammary tumor virus (MMTV) is a retrovirus which can induce mammary carcinomas in mice late in life by activation of proto-oncogenes after integration in their vicinity. Surprisingly, it requires a functional immune system to achieve efficient infection of the mammary gland. This requirement became clear when it was discovered that it has developed strategies to exploit the immune response. Instead of escaping immune detection, it induces a vigorous polyclonal T-B interaction which is required to induce a chronic infection. This is achieved by activating and then infecting antigen presenting cells (B cells), expressing a superantigen on their cell surface and triggering unlimited help by the large number of superantigen-specific T cells. The end result of this strong T-B interaction is the proliferation and differentiation of the infected B cells leading to their long term survival.
Insights
Mouse mammary tumor virus (MMTV) exploits the immune system for infection. It triggers T-B cell interactions, leading to chronic infection and B cell proliferation for long-term survival.
Area of Science:
- Virology
- Immunology
- Oncology
Background:
- Mouse mammary tumor virus (MMTV) is a retrovirus linked to mammary carcinomas in mice.
- MMTV's oncogenic mechanism involves proto-oncogene activation post-integration.
- Efficient MMTV mammary gland infection surprisingly necessitates a functional immune system.
Purpose of the Study:
- To elucidate the mechanisms by which MMTV exploits the host immune system for infection.
- To understand the role of T-B cell interactions in chronic MMTV infection.
- To investigate how MMTV ensures long-term survival of infected cells.
Main Methods:
- Analysis of MMTV's immune evasion and exploitation strategies.
- Investigation of T-B cell interactions induced by MMTV.
- Study of antigen-presenting cell (B cell) activation and infection by MMTV.
- Examination of MMTV superantigen function in T cell activation.
Main Results:
- MMTV has evolved strategies to exploit, rather than evade, immune detection.
- The virus induces a vigorous polyclonal T-B cell interaction essential for chronic infection.
- MMTV activates and infects antigen-presenting B cells, expressing a superantigen.
- This leads to extensive T cell help, promoting proliferation and differentiation of infected B cells.
Conclusions:
- MMTV's oncogenesis is intricately linked to its manipulation of the immune response.
- The virus establishes chronic infection by hijacking T-B cell interactions for B cell survival.
- Understanding these viral-host immune dynamics is crucial for MMTV-related research.
