Abstract:
:CC-chemokine receptor (CCR)-5 is the principal coreceptor for the entry of macrophage (M)-tropic HIV-1 viruses into a cell, while CXC-chemokine receptor (CXCR)-4 is the principal coreceptor for T cell line (T)-tropic HIV-1. In this study, 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. The lymphocytes with the phenotypic knock-out of CCR-5 and CXCR-4 were found broadly to 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 to our knowledge, is the first to demonstrate 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.
journal_name
Gene Therjournal_title
Gene therapyauthors
Bai X,Chen JD,Yang AG,Torti F,Chen SYdoi
10.1038/sj.gt.3300667subject
Has Abstractpub_date
1998-07-01 00:00:00pages
984-94issue
7eissn
0969-7128issn
1476-5462journal_volume
5pub_type
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