A novel membrane protein is a mouse mammary tumor virus receptor
T V Golovkina1, J Dzuris, B van den Hoogen
1Department of Microbiology/Cancer Center, University of Pennsylvania, Philadelphia 19104-6142, USA.
Abstract:
Mouse mammary tumor virus (MMTV) infects a number of different cell types, including mammary gland and lymphoid cells, in vivo. To identify the cellular receptor for this virus, a mouse cDNA expression library was transfected into Cos-7 monkey kidney cells, and those transfected cells able to bind virus were selected by using antibody against the virus's cell surface envelope protein, gp52. One clone isolated from a library prepared from newborn thymus RNA, called MTVR, was able to confer virus binding to both monkey and human cells; this binding was blocked by anti-MTVR antibody. Moreover, transfection of MTVR into CV1 cells rendered them susceptible to infection by a murine leukemia virus-based retrovirus vector pseudotyped with the MMTV envelope protein. An epitope-tagged MTVR cofractionated with cellular membranes. Coimmunoprecipitation of the MMTV envelope protein and a MTVR-rabbit Fc fusion protein showed that these two proteins bound to each other. The MTVR sequence clone is unique, shows no homology to known membrane proteins, and is transcribed in many tissues.
Insights
Researchers identified the Mouse Mammary Tumor Virus Receptor (MTVR) as a key cellular component for MMTV infection. This novel protein facilitates virus binding and entry into various cell types.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Mouse mammary tumor virus (MMTV) infects mammary gland and lymphoid cells.
- Identifying the cellular receptor is crucial for understanding MMTV infection pathways.
Purpose of the Study:
- To identify the cellular receptor for Mouse Mammary Tumor Virus (MMTV).
Main Methods:
- A mouse cDNA expression library was transfected into Cos-7 cells.
- Cells binding MMTV were selected using an antibody against the viral envelope protein gp52.
- The MMTV Receptor (MTVR) gene was isolated and characterized.
Main Results:
- A novel gene, MTVR, was identified that confers MMTV binding to monkey and human cells.
- MTVR-mediated binding was blocked by anti-MTVR antibodies.
- Cells expressing MTVR became susceptible to infection by MMTV envelope pseudotyped retroviral vectors.
- MTVR cofractionated with cellular membranes and directly bound the MMTV envelope protein.
Conclusions:
- MTVR is a novel cellular receptor for MMTV.
- MTVR plays a critical role in MMTV cell entry.
- The MTVR sequence is unique and expressed in multiple tissues.
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