IL-13 and TNF-alpha 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.
Enviado por Luis Montaner el
Título | IL-13 and TNF-alpha 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. |
Publication Type | Journal Article |
Year of Publication | 2000 |
Autores | Bailer, RT, Lee, B, Montaner, LJ |
Journal | Eur J Immunol |
Volume | 30 |
Issue | 5 |
Pagination | 1340-9 |
Date Published | 2000 May |
ISSN | 0014-2980 |
Palabras clave | Antigens, CD4, Cells, Cultured, Drug Synergism, Gene Expression Regulation, Viral, HIV-1, Humans, Interleukin-13, Macrophages, Receptors, CCR5, Receptors, CXCR4, Tumor Necrosis Factor-alpha, Virus Replication |
Abstract | We show that IL-13 in the presence of TNF-alpha 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-1(89.6) (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 (approximately 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-alpha, 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-alpha. In conclusion, our data suggest that IL-13 is a powerful counter-regulatory agent against TNF-alpha-induced HIV-1 expression while also acting with TNF-alpha in inhibiting de novo infection of macrophages. |
Alternate Journal | Eur. J. Immunol. |
PubMed ID | 10820380 |
Grant List | AI40379 / AI / NIAID NIH HHS / United States CA09171 / CA / NCI NIH HHS / United States K08 HL03923-02 / HL / NHLBI NIH HHS / United States |