Hadac Elizabeth M, Peng Kah-Whye, Nakamura Takafumi, Russell Stephen J
Molecular Medicine Program, Mayo Clinic Rochester, Rochester, MN 55905, USA.
Virology. 2004 Nov 24;329(2):217-25. doi: 10.1016/j.virol.2004.08.036.
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.
受体特异性是病毒嗜性的关键决定因素，但病毒转向替代受体的能力尚未得到广泛研究。在此，我们改造了一种减毒麻疹病毒的附着蛋白，并生成了真正重新靶向的病毒，这些病毒对天然受体CD46和信号淋巴细胞激活分子（SLAM）无反应，但能通过替代细胞受体——表皮生长因子受体或CD38高效且专一性地传播。在多次连续传代过程中，改造后的受体嗜性得以稳定维持，不会恢复到使用天然受体，即使在同时提供天然受体和替代受体选择的细胞上也是如此。我们得出结论，副粘病毒具有非常灵活且适应性强的进入机制。
