Interferon-inducible protein (IFI) 16 regulates Chikungunya and Zika virus infection in human skin fibroblasts
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Date
2019-06-27
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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.
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Keywords
Chikungunya virus, Zika virus, IFI16, Human skin fibroblasts, Antiviral