Human cytomegalovirus-encoded US9 targets MAVS and STING signaling to evade type i interferon immune responses

Hyun Jin Choi, Areum Park, Sujin Kang, Eunhye Lee, Taeyun A. Lee, Eun A. Ra, Jiseon Lee, Sungwook Lee, Boyoun Park

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Human cytomegalovirus (HCMV) has evolved sophisticated immune evasion mechanismsthat target both the innate and adaptive immune responses. However, how HCMV encodedproteins are involved in this immune escape is not clear. Here, we show that HCMV glycoproteinUS9 inhibits the IFN-B response by targeting the mitochondrial antiviral-signalingprotein (MAVS) and stimulator of interferon genes (STING)-mediated signaling pathways.US9 accumulation in mitochondria attenuates the mitochondrial membrane potential, leadingto promotion of MAVS leakage from the mitochondria. Furthermore, US9 disrupts STINGoligomerization and STING-TBK1 association through competitive interaction. Intriguingly,US9 blocks interferon regulatory factor 3 (IRF3) nuclear translocation and its cytoplasmicdomain is essential for inhibiting IRF3 activation. Mutant HCMV lacking US7-16 is impaired inantagonism of MAVS/STING-mediated IFN-B expression, an effect that is reversible by theintroduction of US9. Our findings indicate that HCMV US9 is an antagonist of IFN signaling topersistently evade host innate antiviral responses.

Original languageEnglish
Article number125
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this