Cosset F L, Morling F J, Takeuchi Y, Weiss R A, Collins M K, Russell S J
Institute of Cancer Research: Chester Beatty Laboratories, London, United Kingdom.
J Virol. 1995 Oct;69(10):6314-22. doi: 10.1128/JVI.69.10.6314-6322.1995.
We have engineered ecotropic Moloney murine leukemia virus-derived envelopes targeted to cell surface molecules expressed on human cells by the N-terminal insertion of polypeptides able to bind either Ram-1 phosphate transporter (the first 208 amino acids of amphotropic murine leukemia virus surface protein) or epidermal growth factor receptor (EGFR) (the 53 amino acids of EGF). Both envelopes were correctly processed and incorporated into viral particles. Virions carrying these envelopes could specifically bind the new cell surface receptors. Virions targeted to Ram-1 could infect human cells, although the efficiency was reduced compared with that of virions carrying wild-type amphotropic murine leukemia virus envelopes. The infectivity of virions targeted to EGFR was blocked at a postbinding step, and our results suggest that EGFR-bound virions were rapidly trafficked to lysosomes. These data suggest that retroviruses require specific properties of cell surface molecules to allow the release of viral cores into the correct cell compartment.
我们构建了嗜亲性莫洛尼鼠白血病病毒衍生的包膜，通过在N端插入能够结合Ram-1磷酸转运蛋白（嗜异性鼠白血病病毒表面蛋白的前208个氨基酸）或表皮生长因子受体（EGFR）（EGF的53个氨基酸）的多肽，使其靶向人类细胞上表达的细胞表面分子。两种包膜均被正确加工并整合到病毒颗粒中。携带这些包膜的病毒粒子能够特异性结合新的细胞表面受体。靶向Ram-1的病毒粒子能够感染人类细胞，尽管与携带野生型嗜异性鼠白血病病毒包膜的病毒粒子相比，感染效率有所降低。靶向EGFR的病毒粒子的感染性在结合后步骤被阻断，我们的结果表明，与EGFR结合的病毒粒子迅速被转运至溶酶体。这些数据表明，逆转录病毒需要细胞表面分子的特定特性，以使病毒核心释放到正确的细胞区室中。
