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

Nature Medicine volume 3, pages 1110–1116 (1997)Cite this article

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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  1. Si-Yi Chen: Correspondence should be addressed to S.-Y.Z.

Authors and Affiliations

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

    Ji-Dai Chen, Xuefan Bai, An-Gang Yang, Yanping Cong & Si-Yi Chen

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Chen, JD., Bai, X., Yang, AG. et al. Inactivation of HIV-1 chemokine co-receptor CXCR-4 by a novel intrakine strategy. Nat Med 3, 1110–1116 (1997). https://doi.org/10.1038/nm1097-1110

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