Related Experiment Videos
Reengineering paramyxovirus tropism
Elizabeth M Hadac1, Kah-Whye Peng, Takafumi Nakamura
1Molecular Medicine Program, Mayo Clinic Rochester, Rochester, MN 55905, USA.
Virology
|November 3, 2004
Summary
Measles viruses engineered to use new receptors, like epidermal growth factor receptor, show stable tropism switching. This demonstrates the remarkable flexibility of paramyxovirus entry mechanisms.
Area of Science:
- Virology
- Molecular Biology
- Cellular Biology
Background:
- Viral tropism is dictated by receptor specificity.
- The ability of viruses to switch to alternative receptors is not well understood.
- Measles virus typically uses CD46 and SLAM receptors.
Purpose of the Study:
- To engineer measles virus to utilize alternative cellular receptors.
- To investigate the stability of engineered receptor tropism.
- To assess the adaptability of paramyxovirus entry mechanisms.
Main Methods:
- Engineering the attachment protein of an attenuated measles virus.
- Generating retargeted viruses blind to native receptors (CD46, SLAM).
- Propagating engineered viruses on cells expressing alternative receptors (epidermal growth factor receptor, CD38) and assessing tropism stability through serial passage.
Main Results:
- Successfully generated measles viruses retargeted to epidermal growth factor receptor or CD38.
- Engineered tropisms were efficiently and exclusively maintained.
- Stable receptor tropism was observed over multiple serial passages without reversion, even when native receptors were present.
Conclusions:
- Paramyxoviruses possess highly flexible and adaptable entry mechanisms.
- Engineered receptor tropism can be stably maintained, offering insights into viral evolution.
- This study highlights the potential for engineering viral tropism for research and therapeutic applications.