Varicella-Zoster Virus ORF39 Transmembrane Protein Suppresses Interferon-Beta Promoter Activation by Interacting with STING

Gwang Myeong Lee, Shuang Gong, Seong Wook Seo, Hyemin Ko, Woo Chang Chung, Jihyun Lee, Ok Sarah Shin, Jin Hyun Ahn

Research output: Contribution to journalArticlepeer-review

Abstract

Varicella-Zoster virus (VZV) causes varicella in primary infection of children and zoster during reactivation in adults. Type I interferon (IFN) signaling suppresses VZV growth, and stimulator of interferon genes (STING) plays an important role in anti-VZV responses by regulating type I IFN signaling. VZV-encoded proteins are shown to inhibit STING-mediated activation of the IFN-β promoter. However, the mechanisms by which VZV regulates STING-mediated signaling pathways are largely unknown. In this study, we demonstrate that the transmembrane protein encoded by VZV open reading frame (ORF) 39 suppresses STING-mediated IFN-β production by interacting with STING. In IFN-β promoter reporter assays, ORF39 protein (ORF39p) inhibited STING-mediated activation of the IFN-β promoter. ORF39p interacted with STING in co-transfection assays, and this interaction was comparable to that of STING dimerization. The cytoplasmic N-terminal 73 amino acids region of ORF39P was not necessary for ORF39 binding and suppression of STING-mediated IFN-β activation. ORF39p also formed a complex containing both STING and TBK1. A recombinant VZV expressing HA-tagged ORF39 was produced using bacmid mutagenesis and showed similar growth to its parent virus. During HA-ORF39 virus infection, the expression level of STING was markedly reduced, and HA-ORF39 interacted with STING. Moreover, HA-ORF39 also colocalized with glycoprotein K (encoded by ORF5) and STING at the Golgi during virus infection. Our results demonstrate that the transmembrane protein ORF39p of VZV plays a role in evading the type I IFN responses by suppressing STING-mediated activation of the IFN-β promoter.

Original languageEnglish
Pages (from-to)259-270
Number of pages12
JournalJournal of Microbiology
Volume61
Issue number2
DOIs
Publication statusPublished - 2023 Feb
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Microbiological Society of Korea.

Keywords

  • Interferon
  • ORF39
  • STING
  • VZV

ASJC Scopus subject areas

  • Microbiology
  • Applied Microbiology and Biotechnology

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