Reengineering paramyxovirus tropism

Reengineering paramyxovirus tropism
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DOI:
10.1016/j.virol.2004.08.036
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发表时间:
2004-11-24
期刊:
影响因子:
3.7
通讯作者:
Russell, SJ
Russell, SJ
中科院分区:
医学3区
文献类型:
--
作者:
Hadac, EM;Peng, KW;Russell, SJ

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受体特异性是病毒嗜性的关键决定因素,但病毒转换为替代受体的能力尚未得到广泛研究。在这里,我们设计了减毒麻疹病毒的附着蛋白,并产生了真正的重靶向病毒,这些病毒对天然受体CD46和SLAM是盲目的,但它们通过替代细胞受体、表皮生长因子受体或CD38有效且排他地传播。在多次连续病毒传代期间,工程化受体向性稳定维持,而不回复到天然受体使用,甚至在提供天然和替代受体两者的选择的细胞上。我们的结论是,副粘病毒有一个非常灵活和适应性强的进入机制。(C)2004爱思唯尔公司All rights reserved.
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. (C) 2004 Elsevier Inc. All rights reserved.