Authors: Wichit, Sineewanlaya
Hamel, Rodolphe
Yainoy, Sakda
Gumpangseth, Nuttamonpat
Panich, Suchawadee
Phuadraksa, Thanawat
Saetear, Phoonthawee
Monteil, Arnaud
Morales Vargas, Ronald
Missé, Dorothée
Title: Interferon-inducible protein (IFI) 16 regulates Chikungunya and Zika virus infection in human skin fibroblasts
Language (ISO): en
Abstract: Chikungunya virus (CHIKV), a re-emerging infectious arbovirus, causes Chikungunya fever that is characterized by fever, skin rash, joint pain, arthralgia and occasionally death. Despite it has been described for 66 years already, neither potential vaccine nor a specific drug is available yet. During CHIKV infection, interferon type I signaling pathway is stimulated and releases hundreds of interferon stimulated genes (ISGs). Our previous study reported that IFI16, a member of ISGs, is up-regulated during CHIKV virus infection and the suppression of the gene resulted in increased virus replication. Furthermore, our group also found that inflammasome activation can inhibit CHIKV infection in human foreskin cells (HFF1). Concomitantly, it has been reported that IFI16 activates the inflammasome to suppress virus infection. Therefore, we have hypothesized that IFI16 could be involved in CHIKV infection. In this study, we confirmed the expression level of IFI16 by Western blotting analysis and found that IFI16 was up-regulated following CHIKV infection in both HFF1 and human embryonic kidney cells. We next investigated its antiviral activity and found that forced expression of IFI16 completely restricted CHIKV infection while endogenous silencing of the gene markedly increased virus replication. Furthermore, we have dis- covered that IFI16 inhibited CHIKV replication, at least, in cell-to-cell transmission as well as the diffusion step. Interestingly, IFI16 also exerted its antiviral activity against Zika virus (ZIKV) infection, the global threat re- emerging virus can cause microcephaly in humans. Taken together, this study provides the first evidence of an antivirus activity of IFI16 during in vitro arbovirus infection, thus expanding its antiviral spectrum that paves the way to further development of antiviral drugs and vaccines.
Subject Headings: Chikungunya virus
Zika virus
IFI16
Human skin fibroblasts
Antiviral
URI: http://hdl.handle.net/2003/38569
http://dx.doi.org/10.17877/DE290R-20488
Issue Date: 2019-06-27
Rights link: https://creativecommons.org/licenses/by/4.0/
Appears in Collections:Original Articles

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