title: 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.
authors.affiliation: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, 510080, China. zhangp36@mail.sysu.edu.cn
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Siyu
authors.initials: S
authors.lastname: Wu
authors.forename: Lietao
authors.initials: L
authors.lastname: Li
authors.forename: Zhaoduan
authors.initials: Z
authors.lastname: Liang
authors.forename: Yuye
authors.initials: Y
authors.lastname: Li
authors.forename: Lianqiang
authors.initials: L
authors.lastname: Feng
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D009033:Culicidae / Q000166:cytology; D003716:Dengue Virus / Q000145:classification / Q000276:immunology* / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000276:immunology / Q000378:metabolism; D008113:Liver Neoplasms; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014779:Virus Replication / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human