Mouse mammary tumor virus infects human cells
Stanislav Indik1, Walter H Günzburg, Brian Salmons
1Research Institute for Virology and Biomedicine, University of Veterinary Medicine, Vienna, Austria.
Abstract:
Mouse mammary tumor virus (MMTV) has long been speculated to be involved in human breast cancer and more recently in human primary biliary cirrhosis. Despite complete proviral sequences markedly homologous to MMTV being identified in human breast cancer tissue, no convincing evidence has been presented to date that MMTV can infect human cells. Using both wild-type and a genetically marked virus (MMTV-EGFP), we show here the successful infection of a number of different human cells by MMTV. Furthermore, infection of human cells is shown to be almost as efficient as the infection of murine mammary epithelial cells. Sequencing of PCR products from integrated proviruses reveals that reverse transcription and integration of the viral genome has occurred as expected. Furthermore, sequencing of two independent MMTV proviral integration sites reveal them to be present only in the human and not in the mouse genome. Infection requires an intact MMTV envelope protein and is blocked either by heat inactivation of the virus or by specific neutralizing anti-MMTV serum, ruling out a nonspecific mechanism of viral transfer. Thus, MMTV can infect human cells and this finding provides a possible explanation for the detection by others of MMTV sequences in human breast cancer patients.
Insights
Mouse mammary tumor virus (MMTV) can now be shown to infect human cells, providing a potential explanation for its suspected role in human breast cancer and other diseases. This study demonstrates MMTV successfully infects various human cell types.
Area of Science:
- Virology
- Oncology
- Human Cell Biology
Background:
- Mouse mammary tumor virus (MMTV) has been implicated in human cancers, particularly breast cancer, and primary biliary cirrhosis.
- Previous research found MMTV-like sequences in human tissues, but lacked definitive proof of MMTV's ability to infect human cells.
Purpose of the Study:
- To investigate and confirm the infectivity of MMTV in various human cell types.
- To provide molecular evidence for MMTV's successful infection and integration into the human genome.
Main Methods:
- Infection of human cells using wild-type and MMTV-EGFP (genetically marked virus).
- Analysis of viral genome reverse transcription and integration using PCR and sequencing.
- Testing infection requirements, including MMTV envelope protein, heat inactivation, and neutralizing antibodies.
Main Results:
- MMTV successfully infected multiple human cell lines with high efficiency, comparable to murine mammary epithelial cells.
- Sequencing confirmed viral reverse transcription and integration into the human genome.
- Integration sites were unique to the human genome, not found in the mouse genome.
- Infection was dependent on an intact MMTV envelope protein and blocked by heat or specific antibodies, confirming a specific infection mechanism.
Conclusions:
- MMTV is capable of infecting human cells, demonstrating a specific and efficient mechanism.
- This finding offers a plausible explanation for the presence of MMTV sequences in human breast cancer patients.
- The study provides crucial evidence linking MMTV to human cellular infection, opening new avenues for research into MMTV-associated diseases.
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