Anti-dengue activity of synthetic peptides increases antiviral interferon-beta genes in LLC-MK2 cells

Abstract

Dengue virus (DV) causes dengue diseases in human via the Aedes mosquitoes. Fatal cases of dengue hemorrhagic fevers show a complication of acute kidney injury. Previous reports revealed that synthetic DV2(413-440), DV2(413-447), and DV2(419-447) peptides inhibit the dengue envelope proteins in Aedes albopictus C6/36 cells, but nothing is known about the effect of these peptides on mammalian cells in relation to adaptive and innate immunities. In this study, the anti-dengue activity of these synthetic peptides in Rhesus monkey kidney LLC-MK2 cells was investigated at the cellular and molecular levels. Moreover, the effects of these synthetic peptides on apoptotic caspase-10, pro-inflammatory interleukin-1beta, tumor necrosis factor-alpha, and antiviral interferon-beta genes in LLC-MK2 cells were also sought. The results revealed the maximum non-toxic doses of DV2 (413-440), DV2 (413-447), and DV2 (419-447) in LLC-MK2 cells, with values of 77.88± 0.52, 47.01±1.32, and 63.82±1.97 µM, respectively. At 25 µM concentration, synthetic DV2 (413-447) and DV2 (419-447) peptides showed 100% plaque inhibition in simultaneous treatment. By contrast, these peptides showed ≤58% plaque inhibition in pre- and post-treatment at 7 days post-incubation. These synthetic peptides also inhibited Dengue 2 virus, apoptotic caspase-10, pro-inflammatory tumor necrosis factor-alpha, and interleukin-1beta genes. On the other hand, these peptides upregulated the antiviral interferon-beta gene in innate immunity. This study is the first report to reveal the anti-dengue activity of synthetic DV2 (413-440), DV2 (413-447), and DV2 (419-447) peptides in adaptive and innate immunity.