STING Is Involved in Antiviral Immune Response against VZV Infection via the Induction of Type I and III IFN Pathways

Ji Ae Kim, Seul Ki Park, Seong Wook Seo, Chan Hee Lee, Ok Sarah Shin

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


Varicella zoster virus (VZV) is a human-restricted α-herpesvirus that exhibits tropism for the skin. The VZV host receptors and downstream signaling pathways responsible for the antiviral innate immune response in the skin are not completely understood. Here, we show that STING mediates an important host defense against VZV infection in dermal cells including human dermal fibroblasts and HaCaT keratinocytes. Inhibition of STING using small interfering-RNA or short hairpin RNA-mediated gene disruption resulted in enhanced viral replication but diminished IRF3 phosphorylation and induction of IFNs and proinflammatory cytokines. Pretreatment with STING agonists resulted in reduced VZV glycoprotein E expression and viral replication. Additionally, using RNA sequencing to analyze dual host and VZV transcriptomes, we identified several host immune genes significantly induced by VZV infection. Furthermore, significant up-regulation of IFN-λ secretion was observed after VZV infection, partly through a STING-dependent pathway; IFN-λ was shown to be crucial for antiviral defense against VZV in human dermal cells. In conclusion, our data provide an important insight into STING-mediated induction of type I and III IFNs and subsequent antiviral signaling pathways that regulate VZV replication in human dermal cells.

Original languageEnglish
Pages (from-to)2101-2109
Number of pages9
JournalJournal of Investigative Dermatology
Issue number10
Publication statusPublished - 2017 Oct
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT & Future Planning (NRF-2016R1C1B2006493), and research funding from Green Cross. We thank Takashi Fujita (Kyoto University, Japan) for sharing plasmids.

Publisher Copyright:
© 2017 The Authors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology


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