淋巴细胞HI V-1辅受体的表型剔除对病毒感染的阻断作用

We utilized a novel intracellular chemokine(intrakine) strategy to co-inactivate genetically both CCR-5 and CXCR-4 in human lymphocytes. The principle of co-inactivation of CCR-5 and CXCR-4 was illustrated by targeting the CC-intrakine and CXC-intrakine to the lumen of the endoplasmic reticulum (ER) for intracellular blockade of the transport of newly synthesized chemokine coreceptors to the cell surface. We constructed bicistronic vectors for CC-intrakine and CXC-intrakine and examined co-expression of them. The lymphocytes with the phenotypic knock-out of CCR-5 and CXCR-4 were found broadly resist the infection of M-tropic, T-tropic and dual-tropic HIV-1 viruses. Moreover, the transduced lymphocytes retained normal cell features, including the responsiveness to mitogen and recall antigen stimulation. Thus, this study demonstrates that genetic co-inactivation of the M- and T-tropic HIV-1 principal coreceptors in lymphocytes or other cells could be a viable strategy for the long-term control of HIV-1 infection.

AI DS 是严重危害人类健康的疾病，其化疗目前仍无突破性进展，各种基因治疗也举步为琛Ｐ陆⑾值那骰蜃邮芴錍X CR -4和CC R-5是HI V-1感染重要的辅受体。本研究拟通齛和类趋化因子SD F与RAN TES的细胞内表达以及表达产物与HI V-1 辅受体的结合，从细胞表型上剔除两类辅受体，从而实现同时阻断两种嗜性病毒感染的目的，为AI DS 的治疗开偾椎耐揪丁