Cytokines Modulate HIV Replication and the Activity of Antiviral Drugs in Cells of Monocyte/Macrophage Lineage

Abstract

The role of cytokines in modulating either replication of HIV, the cause of acquired immunodeficiency syndrome (AIDS), or the activity of antiviral drugs, is not yet fully understood. We then undertook an investigation to evaluate viral replication in cells of monocyte/macrophage lineage (M/M) exposed to granulocyte-macrophage colony stimulating factor (GM-CSF) or macrophage-colony stimulating factor (M-CSF) in combination with various anti-HIV drugs. We found that GM-CSF and M-CSF potently enhance HIV replication in M/M. Moreover, the antiviral activity of 2’, 3’-dideoxyadenosine (ddA), a prototype drug working as reverse transcriptase inhibitor, is decreased by GM-CSF. By contrast, neither GM-CSF nor M-CSF interfere with the antiviral activity of soluble CD4, and antisense phosphorothioate oligonucleotides against rev gene of the virus; these two molecules inhibit viral binding on CD4 molecule and viral translation respectively. Cytokines such as GM-CSF and M-CSF are able to modulate some immune functions impaired by HIV in AIDS patients. Moreover, even in the case of reduction of antiviral activity of ddA by GM-CSF, complete inhibition of viral replication can be obtained by 10 uM ddA, a concentration similar to that achieved in patients treated with 2’, 3’-dideoxyinosine (ddI, the active moiety of ddA).