Proceedings of the National Academy of Sciences · 1997 · 109 citations · 41 references
Life SciencesImmunologyMolecular BiologyCell SignalingHiv PreventionMolecular ImmunologyAntiretroviral TherapyAntiviral ImmunityChemokine NetworksChemokine SignalingImmune Cell SignalingMacrophage BiologyChemokine BiologyChemokine FunctionEndoplasmic Reticulum TargetingG Protein-coupled Chemokine ReceptorsGene KnockoutHiv Antiretroviral TherapyHiv Infection ModelsKnockout Animals
A genetic defect in a CC-chemokine receptor (CCR)-5, the principal coreceptor for the macrophage-tropic HIV type 1 (HIV-1), recently was found to naturally protect CCR-5-defective, but healthy, individuals from HIV-1 infection. In this study, we mimic the natural resistance of the CCR-5-defective individuals by designing a strategy to phenotypically knock out CCR-5. The inactivation of the CCR-5 coreceptor is accomplished by targeting a modified CC-chemokine to the endoplasmic reticulum to block the surface expression of newly synthesized CCR-5. The lymphocytes transduced to express the intracellular chemokine, termed "intrakine," were found to be viable and resistant to macrophage-tropic HIV-1 infection. Thus, this gene-based intrakine strategy targeted at the conserved cellular receptor for the prevention of HIV-1 entry should have significant advantages over currently described approaches for HIV-1 therapy.
41
Identification of a major co-receptor for primary isolates of HIV-1
Hongkui Deng, Rong Liu, Wilfried Ellmeier et al. · Nature · 1996 · 3.7K citations
HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5
Tatjana Dragic, Virginia Litwin, Graham P. Allaway et al. · Nature · 1996 · 3.2K citations