Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist - PubMed (original) (raw)
Comparative Study
. 1997 Apr 11;276(5310):276-9.
doi: 10.1126/science.276.5310.276.
Affiliations
- PMID: 9092481
- DOI: 10.1126/science.276.5310.276
Comparative Study
Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist
G Simmons et al. Science. 1997.
Abstract
The chemokine receptors CXCR4 and CCR5 have recently been shown to act as coreceptors, in concert with CD4, for human immunodeficiency virus-type 1 (HIV-1) infection. RANTES and other chemokines that interact with CCR5 and block infection of peripheral blood mononuclear cell cultures inhibit infection of primary macrophages inefficiently at best. If used to treat HIV-1-infected individuals, these chemokines could fail to influence HIV replication in nonlymphocyte compartments while promoting unwanted inflammatory side effects. A derivative of RANTES that was created by chemical modification of the amino terminus, aminooxypentane (AOP)-RANTES, did not induce chemotaxis and was a subnanomolar antagonist of CCR5 function in monocytes. It potently inhibited infection of diverse cell types (including macrophages and lymphocytes) by nonsyncytium-inducing, macrophage-tropic HIV-1 strains. Thus, activation of cells by chemokines is not a prerequisite for the inhibition of viral uptake and replication. Chemokine receptor antagonists like AOP-RANTES that achieve full receptor occupancy at nanomolar concentrations are strong candidates for the therapy of HIV-1-infected individuals.
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