RETROVIRAL RETARGETING BY ENVELOPES EXPRESSING AN N-TERMINAL BINDING DOMAIN
RETROVIRAL RETARGETING BY ENVELOPES EXPRESSING AN N-TERMINAL BINDING DOMAIN
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DOI：
10.1128/jvi.69.10.6314-6322.1995
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发表时间：
1995-10-01
影响因子：
5.4
通讯作者：
RUSSELL, SJ
中科院分区：
文献类型：
--
作者：
COSSET, FL;MORLING, FJ;RUSSELL, SJ
我们通过N端插入能够与Ram-1磷酸转运蛋白(两性小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(EGF的53个氨基酸)结合的多肽，设计出了针对人类细胞表达的细胞表面分子的生态型Moloney小鼠白血病病毒包膜。这两个信封都经过了正确的处理，并被合并到病毒颗粒中。携带这些包膜的病毒粒子可以特异性地结合新的细胞表面受体。靶向Ram-1的病毒粒子可以感染人类细胞，尽管与携带野生型两性小鼠白血病病毒包膜的病毒粒子相比，其效率有所降低。针对EGFR的病毒粒子的感染性在结合后的步骤中被阻断，我们的结果表明，与EGFR结合的病毒粒子迅速被运送到溶酶体。这些数据表明，逆转录病毒需要细胞表面分子的特殊性质，才能将病毒核心释放到正确的细胞室。
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.