Adjuvant PIKA protects hepatoma cells from dengue virus infection by promoting a TBK-1-dependent innate immune response

Abstract

Our study presents a first investigation of the effect of the adjuvant PIKA on dengue virus (DENV) replication. PIKA pretreatment decreased the levels of DENV serotype 2 (DENV2) mRNA, protein and viral particles in the hepatoma cell line HepG2. Treatment with PIKA simultaneously with DENV2 infection, but not after infection, resulted in a protective effect. Significant induction of type I and type III interferons (IFNs), as well as interferon-stimulated genes was detected in PIKA-pretreated cells. Neutralization of IFN-β partially restored the replication levels of DENV2 in PIKA-pretreated cells, suggesting that IFN-β is one of the mediators involved in the antiviral action of PIKA. Additionally, blockade of TBK-1 signaling largely restored the IFN induction and viral suppression effects mediated by PIKA, further illustrating that PIKA plays its anti-DENV role by promoting innate immunity. These findings suggest that PIKA is an attractive agent to be used in the prevention of DENV diseases.

Review of Current Dengue Treatment and Therapeutics in Development

“…Along a similar vein, Diwaker et al have recently identified the RIG-I inducer Rhodiola as an inhibitor of DENV in human peripheral blood mononuclear cells and the human monocytic cell THP1 cell line, when administered 2 hours after DENV infection [117]. Et al showed that TLR3 activation through administration of the dsRNA compound PIKA prior to DENV infection decreased DENV infection of HepG2 cells [118].…”