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 Shin

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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
Volume137
Issue number10
DOIs
Publication statusPublished - 2017 Oct 1

Fingerprint

Human Herpesvirus 3
Virus Diseases
Viruses
Antiviral Agents
Skin
Small Interfering RNA
Genes
RNA Sequence Analysis
Virus Receptors
Phosphorylation
Tropism
Herpesviridae
Fibroblasts
Virus Replication
Keratinocytes
Transcriptome
Innate Immunity
Glycoproteins
Up-Regulation
RNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

STING Is Involved in Antiviral Immune Response against VZV Infection via the Induction of Type I and III IFN Pathways. / Kim, Ji Ae; Park, Seul Ki; Seo, Seong Wook; Lee, Chan Hee; Shin, Ok.

In: Journal of Investigative Dermatology, Vol. 137, No. 10, 01.10.2017, p. 2101-2109.

Research output: Contribution to journalArticle

Kim, Ji Ae ; Park, Seul Ki ; Seo, Seong Wook ; Lee, Chan Hee ; Shin, Ok. / STING Is Involved in Antiviral Immune Response against VZV Infection via the Induction of Type I and III IFN Pathways. In: Journal of Investigative Dermatology. 2017 ; Vol. 137, No. 10. pp. 2101-2109.
@article{e073bd432e3b4305bd877a6c662634ac,
title = "STING Is Involved in Antiviral Immune Response against VZV Infection via the Induction of Type I and III IFN Pathways",
abstract = "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.",
author = "Kim, {Ji Ae} and Park, {Seul Ki} and Seo, {Seong Wook} and Lee, {Chan Hee} and Ok Shin",
year = "2017",
month = "10",
day = "1",
doi = "10.1016/j.jid.2017.03.041",
language = "English",
volume = "137",
pages = "2101--2109",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - STING Is Involved in Antiviral Immune Response against VZV Infection via the Induction of Type I and III IFN Pathways

AU - Kim, Ji Ae

AU - Park, Seul Ki

AU - Seo, Seong Wook

AU - Lee, Chan Hee

AU - Shin, Ok

PY - 2017/10/1

Y1 - 2017/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85031018074&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031018074&partnerID=8YFLogxK

U2 - 10.1016/j.jid.2017.03.041

DO - 10.1016/j.jid.2017.03.041

M3 - Article

C2 - 28647346

AN - SCOPUS:85031018074

VL - 137

SP - 2101

EP - 2109

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 10

ER -