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Nat Med. 1997 Oct;3(10):1110-6.

Inactivation of HIV-1 chemokine co-receptor CXCR-4 by a novel intrakine strategy.

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1
Department of Cancer Biology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA.

Abstract

CXC-chemokine receptor (CXCR)-4/fusin, a newly discovered co-receptor for T-cell line (T)-tropic HIV-1 virus, plays a critical role in T-tropic virus fusion and entry into permissive cells. The occurrence of T-tropic HIV viruses is associated with CD4-positive cell decline and progression to AIDS, suggesting that the T-tropic HIV-1 contributes to AIDS pathogenesis. In this study, we used a novel strategy to inactivate CXCR-4 by targeting a modified CXC-chemokine to the endoplasmic reticulum (ER) to block the surface expression of newly synthesized CXCR-4. The genetically modified lymphocytes expressing this intracellular chemokine, termed "intrakine", are immune to T-tropic virus infection and appear to retain normal biological features. Thus, this genetic intrakine strategy is uniquely targeted at the conserved cellular receptor for the prevention of HIV-1 entry and may be developed into an effective treatment for HIV-1 infection and AIDS.

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PMID:
9334722
DOI:
10.1038/nm1097-1110
[Indexed for MEDLINE]

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