Effect of beta-chemokines on human immunodeficiency virus type 1 replication, binding, uncoating, and CCR5 receptor expression in human monocyte-derived macrophages

Objectives: We examined the effect and time of addition of beta-chemokines on human immunodeficiency virus type 1 (HIV-1) replication, binding, and un coating in human macrophages and measured CCR5 receptor expression during v irus binding and uncoating. Methods: Macrophages were treated with beta-chemokines before infection, at infection, or postinfection, and virus replication was determined by p24 a ntigen level. Binding and uncoating of (35)[S]-methionine-labeled HIV-1 was measured. CCR5 expression was determined by flow cytometry. Results: The beta-chemokines potently inhibited virus replication. The stro ngest inhibition occurred when cultures were pretreated and maintained with beta-chemokines. beta-Chemokines also caused strong inhibition of viral un coating and a considerable decrease in CCR5 expression during uncoating. Conclusions: CCR5 receptors appear to be internalized and recycled to the c ell surfaces during HIV entry. The downregulation of CCR5 expression by bet a-chemokines during virus uncoating probably accounts for the reduction in virus uncoating (entry) and hence in virus replication.