Interferon γ and interleukin 6 modulate the susceptibility of macrophages to human immunodeficiency virus type 1 infection
| Autor: | Rolf E. Taffs, Cheryl K. Lapham, Jody Manischewitz, Marina Zaitseva, Hana Golding, Tatiana Romantseva, Shirley Lee, Lisa King |
|---|---|
| Rok vydání: | 2000 |
| Předmět: | |
| Zdroj: | Blood. 96:3109-3117 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v96.9.3109 |
| Popis: | The effect of interferon γ (IFN-γ) and interleukin 6 (IL-6) on infection of macrophages with human immunodeficiency virus type 1 (HIV-1) was investigated. By using a polymerase chain reaction–based viral entry assay and viral infectivity assay, it was demonstrated that IL-6 and IFN-γ augmented susceptibility of monocyte-derived macrophages (MDMs) to infection with T-cell tropic CXCR4-utilizing (X4) HIV-1 strains. Consistent with this finding, IFN-γ and IL-6 augmented fusion of MDMs with T-tropic envelope-expressing cells. The enhanced fusion of cytokine-treated MDMs with T-tropic envelopes was inhibited by the CXCR4 ligand, SDF-1, and by T22 peptide. IFN-γ and IL-6 did not affect expression of surface CXCR4 or SDF-1–induced Ca++ flux in MDMs. In contrast to the effect of IFN-γ on the infection of MDMs with X4 strains, IFN-γ inhibited viral entry and productive infection of MDMs with macrophage-tropic (M-tropic) HIV-1. Consistent with this finding, IFN-γ induced a decrease in fusion with M-tropic envelopes that correlated with a modest reduction in surface CCR5 and CD4 on MDMs. It was further demonstrated that macrophage inflammatory protein (MIP)-1α and MIP-β secreted by cytokine-treated MDMs augmented their fusion with T-tropic–expressing cells and inhibited their fusion with M-tropic envelope-expressing cells. These data indicate that proinflammatory cytokines, which are produced during opportunistic infections or sexually transmitted diseases, may predispose macrophages to infection with X4 strains that, in turn, could accelerate disease progression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|