IL‐13 and TNF‐α  inhibit dual‐tropic HIV‐1 in primary macrophages by reduction of surface expression of CD4, chemokine receptors CCR5, CXCR4 and post‐entry viral gene expression

We show that IL‐13 in the presence of TNF‐α effected an equal or greater antiviral activity against a dual‐tropic HIV‐1 (R5X4) in macrophages. A temporary or continued exposure of macrophages to both cytokines significantly decreased the infection and replication of R5X4 HIV‐189.6 (median, 128‐fold, n = 9, p = 0.024) in macrophages as compared to untreated controls when analyzed over six decreasing multiplicities of infection. A quantitative flow cytometric assay revealed that IL‐13 induced a significant (∼ 50 %) reduction in the number of CD4 and CC chemokine receptor 5 (CCR5) antibody binding sites while completely abrogating surface expression of CXC chemokine receptor 4 (CXCR4). In the presence of IL‐13 and TNF‐α, expression of CCR5 was completely abrogated while the expression of CD4 and CXCR4 remained significantly reduced as compared to untreated controls. A reduction in CD4 and HIV‐1 coreceptors was associated with a decrease in reverse‐transcribed viral DNA at 24 h post‐infection. Quantification of viral gene expression using amphotropic MLV Env pseudotyped luciferase reporter viruses suggested that IL‐13 inhibited HIV‐1 gene expression within 24 h by up to 90 % in the presence or absence of TNF‐α. In conclusion, our data suggest that IL‐13 is a powerful counter‐regulatory agent against TNF‐α‐induced HIV‐1 expression while also acting with TNF‐α in inhibiting de novo infection of macrophages.