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

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Jundee Rabablert
Promsin Masrinoul
Sutee Yoksan
Supoth Rajakam
Supanyika Sengsai
Korakot Changirakul
Prayad Sangngam
Sunee Techaarpornkul
Sittiruk Roytrakul

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.

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