Effect of beta-chemokines on human immunodeficiency virus type 1 replication, binding, uncoating, and CCR5 receptor expression in human monocyte-derived macrophages.
OBJECTIVE
We examined the effect and time of addition of beta-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.


METHODS
Macrophages were treated with beta-chemokines before infection, at infection, or postinfection, and virus replication was determined by p24 antigen 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 strongest inhibition occurred when cultures were pretreated and maintained with beta-chemokines. Beta-chemokines also caused strong inhibition of viral uncoating and a considerable decrease in CCR5 expression during uncoating.


CONCLUSIONS
CCR5 receptors appear to be internalized and recycled to the cell surfaces during HIV entry. The down-regulation of CCR5 expression by beta-chemokines during virus uncoating probably accounts for the reduction in virus uncoating (entry) and hence in virus replication.
Jiang
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Y
School of Public Health, University of Alabama at Birmingham, 35294-0022, USA.
Jolly
P E
PE
D015704:CD4 Antigens; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology*; D019742:Chemokines, CC / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D008715:Methionine / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D013462:Sulfur Radioisotopes; D014779:Virus Replication / Q000187:drug effects*
D015704:CD4 Antigens; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D013462:Sulfur Radioisotopes; D008715:Methionine