Interferon-inducible protein (IFI) 16 regulates Chikungunya and Zika virus infection in human skin fibroblasts

Authors

  • Sineewanlaya Wichit Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, 73170, Thailand, E-mail: sineewanlaya.wic@mahidol.ac.th, Telephone: +66-92-705-9933, Fax: +66 2 441 4380
  • Rodolphe Hamel Laboratoire MIVEGEC, IRD-CNRS-University of Montpellier, 34000, Montpellier, France; Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand
  • Sakda Yainoy Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, 73170, Thailand
  • Nuttamonpat Gumpangseth Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, 73170, Thailand
  • Suchawadee Panich Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, 73170, Thailand
  • Thanawat Phuadraksa Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, 73170, Thailand
  • Phoonthawee Saetear Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
  • Arnaud Monteil Plateforme de Vectorologie, BioCampus, Univ. Montpellier, CNRS, INSERM, 34094, Montpellier, France
  • Ronald Morales Vargas Department of Medical Entomology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand
  • Dorothée Missé Laboratoire MIVEGEC, IRD-CNRS-University of Montpellier, 34000, Montpellier, France

DOI:

https://doi.org/10.17179/excli2019-1271

Keywords:

Chikungunya virus, Zika virus, IFI16, human skin fibroblasts, antiviral

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 discovered 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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Published

2019-06-27

How to Cite

Wichit, S., Hamel, R., Yainoy, S., Gumpangseth, N., Panich, S., Phuadraksa, T., … Missé, D. (2019). Interferon-inducible protein (IFI) 16 regulates Chikungunya and Zika virus infection in human skin fibroblasts. EXCLI Journal, 18, 467–476. https://doi.org/10.17179/excli2019-1271

Issue

Vol. 18 (2019)

Section

Original articles

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