Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection

Abstract

BackgroundBovine dialyzable leukocyte extract (bDLE) is derived from immune leukocytes obtained from bovine spleen. DLE has demonstrated to reduce transcription of Human Immunodeficiency Virus Type 1 (HIV-1) and inactivate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Therefore, we decided to clarify the mode of antiviral action of bDLE on the inhibition of HIV-1 infection through a panel of antiviral assays.ResultsThe cytotoxicity, HIV-1 inhibition activity, residual infectivity of bDLE in HIV-1, time of addition experiments, fusion inhibition of bDLE for fusogenic cells and the duration of cell protection even after the removal of bDLE were all assessed in order to discover more about the mode of the antiviral action.HIV-1 infectivity was inhibited by bDLE at doses that were not cytotoxic for HeLa-CD4-LTR-β-gal cells. Pretreatment of HIV-1 with bDLE did not decrease the infectivity of these viral particles. Cell-based fusion assays helped to determine if bDLE could inhibit fusion of Env cells against CD4 cells by membrane fusion and this cell-based fusion was inhibited only when CD4 cells were treated with bDLE. Infection was inhibited in 80% compared with the positive (without EDL) at all viral life cycle stages in the time of addition experiments when bDLE was added at different time points. Finally, a cell-protection assay against HIV-1 infection by bDLE was performed after treating host cells with bDLE for 30 minutes and then removing them from treatment. From 0 to 7 hours after the bDLE was completely removed from the extracellular compartment, HIV-1 was then added to the host cells. The bDLE was found to protect the cells from HIV-1 infection, an effect that was retained for several hours.ConclusionsbDLE acted as an antiviral compound and prevented host cell infection by HIV-1 at all viral life cycle stages. These cell protection effects lingered for hours after the bDLE was removed. Interestingly, bDLE inhibited fusion of fusogenic cells by acting only on CD4 cells. bDLE had no virucidal effect, but could retain its antiviral effect on target cells after it was removed from the extracellular compartment, protecting the cells from infection for hours.bDLE, which has no reported side effects or toxicity in clinical trials, should therefore be further studied to determine its potential use as a therapeutic agent in HIV-1 infection therapy, in combination with known antiretrovirals.

Anti-Inflammatory Effect of Dialyzable Leukocyte Extract in Autoimmune Prostatitis: Evaluation in Animal Model

“…The DLE effects on the immune system include cytokine modulation [27], monocyte activation, macrophage chemotaxis, and natural killer activity enhancement [11]. In vitro, DLE regulates the NF- κ B activity and reduces TNF- α and TGF- B 1 secretion, downregulating the HIV transcription [11].…”

“…For example, Elocalcitol, a vitamin D receptor agonist, decreases the inflammatory process by diminishing the expression of IFN- γ and IL-17 and by inhibiting CD4+ and CD8+ prostate infiltrate in a murine model [7]. Dialyzable Leukocyte Extract (DLE) has been used for the treatment of many inflammatory diseases, like osteoarthritis [8], autoimmune [9], bacterial [10], and viral [11] diseases among others. Pizza et al in 1996 showed that DLE promoted cancer remissions and increased the survival of prostatic cancer patients [12].…”

Dialysable leukocyte extracts in immunotherapy

“…Apart from human leucocytes, TF preparations are obtained from ultrafiltrated animal cryolysed leukocytes or lymphoid organs (lymph nodes and spleen). [16,17,20,30,31] Transfer factor can also be produced in bird eggs. Xu et al [32] have obtained TF from egg yolk which is active against HBV and Hennen and Lisobree [33] have patented a method for producing TF preparations from bird eggs.…”

“…DLE can reduce the transcription of HIV-1 and inactivate the NF-kB signalling pathway. [31] The first clinical trial on a TF preparation for AIDS treatment was conducted by Viza et al [46]. Murine HIVspecific TF was orally administered to three patients for a period of 3À5 months.…”

Immunotherapy with Dialyzable Leukocyte Extracts Containing Transfer Factor

“…Membrane filters with a cutoff of <12 kDa are used in the procedure. Apart from human leucocytes, TF-preparations are obtained from ultrafiltrated animal cryolysed leukocytes or lymphoid organs (lymph nodes and spleen) [17,18,26,31,32].…”