Inactivation of HIV-1 chemokine co-receptor CXCR-4 by a novel intrakine strategy.
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.
Chen
J D
JD
Department of Cancer Biology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA.
Bai
X
X
Yang
A G
AG
Cong
Y
Y
Chen
S Y
SY
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D018925:Chemokines / Q000096:biosynthesis*; D019743:Chemokines, CXC; D003587:Cytomegalovirus; D005822:Genetic Vectors; D015726:Giant Cells; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008214:Lymphocytes / Q000276:immunology*; D016133:Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology; D015728:Receptors, HIV / Q000037:antagonists & inhibitors* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D011993:Recombinant Fusion Proteins