Reengineering paramyxovirus tropism

Receptor specificity is a critical determinant of viral tropism, but the capacity of viruses to switch to alternative receptors has not been extensively studied. Here, we engineered the attachment protein of an attenuated measles virus and generated truly retargeted viruses that are blind to the native receptors CD46 and SLAM, but which propagate efficiently and exclusively via alternative cellular receptors, epidermal growth factor receptor, or CD38. The engineered receptor tropisms were stably maintained during multiple serial virus passage without reversion to native receptor usage, even on cells offering the choice of both native and alternative receptors. We conclude that paramyxoviruses have a remarkably flexible and adaptable entry mechanism.