Poly (I:C), an agonist of toll-like receptor-3, inhibits replication of the Chikungunya virus in BEAS-2B cells

Surapee Anantapreecha,Uamporn Siripanyaphinyo,Uranan Tumkosit,Takeshi Kurosu,Yang Pan,Atchareeya A-nuegoonpipat,Masanori Kameoka,Naokazu Takeda,Yong-Gang Li,Kazuyoshi Ikuta,Nitchakarn Noranate

doi:10.1186/1743-422x-9-114

Surapee Anantapreecha, Uamporn Siripanyaphinyo + Show 9 more

Open Access

https://doi.org/10.1186/1743-422x-9-114

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Abstract

BackgroundDouble-stranded RNA (dsRNA) and its mimic, polyinosinic acid: polycytidylic acid [Poly (I:C)], are recognized by toll-like receptor 3 (TLR3) and induce interferon (IFN)-β in many cell types. Poly (I:C) is the most potent IFN inducer. In in vivo mouse studies, intraperitoneal injection of Poly (I:C) elicited IFN-α/β production and natural killer (NK) cells activation. The TLR3 pathway is suggested to contribute to innate immune responses against many viruses, including influenza virus, respiratory syncytial virus, herpes simplex virus 2, and murine cytomegalovirus. In Chikungunya virus (CHIKV) infection, the viruses are cleared within 7–10 days postinfection before adaptive immune responses emerge. The innate immune response is important for CHIKV clearance.ResultsThe effects of Poly (I:C) on the replication of CHIKV in human bronchial epithelial cells, BEAS-2B, were studied. Poly (I:C) suppressed cytopathic effects (CPE) induced by CHIKV infection in BEAS-2B cells in the presence of Poly (I:C) and inhibited the replication of CHIKV in the cells. The virus titers of Poly (I:C)-treated cells were much lower compared with those of untreated cells. CHIKV infection and Poly (I:C) treatment of BEAS-2B cells induced the production of IFN-β and increased the expression of anti-viral genes, including IFN-α, IFN-β, MxA, and OAS. Both Poly (I:C) and CHIKV infection upregulate the expression of TLR3 in BEAS-2B cells.ConclusionsCHIKV is sensitive to innate immune response induced by Poly (I:C). The inhibition of CHIKV replication by Poly (I:C) may be through the induction of TLR3, which triggers the production of IFNs and other anti-viral genes. The innate immune response is important to clear CHIKV in infected cells.

Highlights

Chikungunya virus (CHIKV), the causative agent for Chikungunya fever, was first described in 1952 during an epidemic in Tanzania, East Africa [1,2]
(I:C) suppressed cytopathic effects (CPE) induced by CHIKV infection BEAS-2B cells were seeded in 6-well plates (1x106 cells/ well) one day before Poly (I:C) treatment
CPE was found in the Poly (I:C)-treated cells at 72 h p.i., it was less significant compared with that of untreated cells (Figure 1), demonstrating that Poly (I:C) treatment appeared to decrease CPE induced by CHIKV infection

Summary

Introduction

Chikungunya virus (CHIKV), the causative agent for Chikungunya fever, was first described in 1952 during an epidemic in Tanzania, East Africa [1,2]. 3–4 million people in the Indian Ocean zone, and it spread to Europe in 2005–2007. As a typical adaptive immune response, such as CHIKV-specific B-cell and T-cell activation, requires at least 1 week for development, the innate immune system seems to control CHIKV infection [23]. Polyinosinic: polycytidylic acid [Poly (I:C)], a synthetic double-stranded RNA (dsRNA) analog, is an immunostimulant that acts as the most potent interferon (IFN) inducer [27]. Double-stranded RNA (dsRNA) and its mimic, polyinosinic acid: polycytidylic acid [Poly (I:C)], are recognized by toll-like receptor 3 (TLR3) and induce interferon (IFN)-β in many cell types. In Chikungunya virus (CHIKV) infection, the viruses are cleared within 7–10 days postinfection before adaptive immune responses emerge.

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