Effect of bgr;-Chemokines on Human Immunodeficiency Virus Type 1 Replication, Binding, Uncoating, and CCR5 Receptor Expression in Human Monocyte-Derived Macrophages

摘要

Objectivescolon;We examined the effect and time of addition of bgr;-chemokines on human immunodeficiency virus type 1 (HIV-1) replication, binding, and uncoating in human macrophages and measured CCR5 receptor expression during virus binding and uncoating.Methodscolon;Macrophages were treated with bgr;-chemokines before infection, at infection, or postinfection, and virus replication was determined by p24 antigen level. Binding and uncoating of35lsqb;Srsqb;-methionine-labeled HIV-1 was measured. CCR5 expression was determined by flow cytometry.Resultscolon;The bgr;-chemokines potently inhibited virus replication. The strongest inhibition occurred when cultures were pretreated and maintained with bgr;-chemokines. bgr;-Chemokines also caused strong inhibition of viral uncoating and a considerable decrease in CCR5 expression during uncoating.Conclusionscolon;CCR5 receptors appear to be internalized and recycled to the cell surfaces during HIV entry. The downregulation of CCR5 expression by bgr;-chemokines during virus uncoating probably accounts for the reduction in virus uncoating (entry) and hence in virus replication.Journal of Human Virology 1999;2:123-132 copy; Lippincott Williams amp; Wilkins, Inc.