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


RESULTS
The 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.


CONCLUSIONS
CHIKV 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.
Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. yonggang@biken.osaka-u.ac.jp
Yong-Gang
YG
Li
Uamporn
U
Siripanyaphinyo
Uranan
U
Tumkosit
Nitchakarn
N
Noranate
Atchareeya
A
A-Nuegoonpipat
Yang
Y
Pan
Masanori
M
Kameoka
Takeshi
T
Kurosu
Kazuyoshi
K
Ikuta
Naokazu
N
Takeda
Surapee
S
Anantapreecha
D002646:Chikungunya virus / Q000187:drug effects / Q000502:physiology*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000821:virology*; D019204:GTP-Binding Proteins; D020869:Gene Expression Profiling; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D064547:Myxovirus Resistance Proteins; D011070:Poly I-C / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000819:agonists*; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; D019204:GTP-Binding Proteins; D011070:Poly I-C