Related Experiment Videos
Transgenic mice expressing human measles virus (MV) receptor CD46 provide cells exhibiting different permissivities
B Horvat1, P Rivailler, G Varior-Krishnan
1Laboratoire d'Immunobiologie Moléculaire, Ecole Normale Supérieure deLyon, UMR 49, CNRS, France.
Abstract:
We have generated transgenic mice ubiquitously expressing the human receptor for measles virus (MV), CD46 (membrane cofactor protein). Various cell types were isolated from these transgenic mice and analyzed for their ability to support MV replication in vitro. Although MV could enter into all CD46-expressing cells, differential susceptibilities to MV infection were detected depending on the cell type. Cell cultures obtained from transgenic lungs and kidneys were found to be permissive of MV infection, since RNA specific for MV genes was detected and viral particles were released, although at a low level. Similarly to human lymphocytes, activated T and B lymphocytes isolated from transgenic mice could support MV replication; virus could enter, transcribe viral RNA, and produce new infectious particles. When expressing viral proteins, lymphocytes down-regulated CD46 from the surface. Interestingly, while activated T lymphocytes from nontransgenic mice did not support MV infection, activated nontransgenic murine B lymphocytes replicated MV as well as transgenic B lymphocytes, suggesting the use of an alternative virus receptor for entry. In contrast to the previous cell types, murine peritoneal and bone marrow-derived macrophages, regardless of whether they were activated, could not support MV replication. Furthermore, although MV entered into macrophages and virus-specific RNA transcription occurred, no virus protein or infectious virus particles could be detected. These results show the importance of the particular cell-type-specific host factors for MV replication in murine cells which may be responsible for the differential permissivity of MV infection.
Insights
Transgenic mice expressing the human measles virus (MV) receptor CD46 showed varied susceptibility to MV infection across cell types. Murine lymphocytes supported MV replication, while macrophages did not, highlighting cell-specific host factors.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Measles virus (MV) entry into cells is primarily mediated by its receptor, CD46.
- Understanding the cellular tropism of MV is crucial for studying viral pathogenesis and developing antiviral strategies.
Purpose of the Study:
- To investigate the permissivity of various murine cell types to measles virus (MV) infection using transgenic mice expressing the human CD46 receptor.
- To identify cell-type-specific host factors influencing MV replication.
Main Methods:
- Generation of transgenic mice ubiquitously expressing human CD46.
- Isolation and in vitro culture of diverse cell types (lungs, kidneys, lymphocytes, macrophages) from transgenic and non-transgenic mice.
- Analysis of MV replication by detecting viral RNA, proteins, and infectious particles.
Main Results:
- Transgenic murine lungs, kidneys, and lymphocytes supported MV replication, with RNA transcription and viral particle release observed.
- Activated lymphocytes from both transgenic and non-transgenic mice supported MV replication, suggesting an alternative receptor in non-transgenic B lymphocytes.
- Murine macrophages, regardless of activation status, could not support MV replication, despite MV entry and RNA transcription, indicating a block in viral protein synthesis or particle assembly.
Conclusions:
- Murine cell-type-specific host factors play a critical role in determining permissivity to measles virus infection.
- Differential susceptibility to MV infection in various murine cell types is not solely dependent on CD46 expression.