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Nat. Commun., Published online: 09 January 2018, 9, Article number: 125 | doi:10.1038/s41467-017-02624-8 Human cytomegalovirus-encoded US9 targets MAVS and STING signaling to evade type I interferon immune responses

Hyun jin Choi¹, Areum Park¹, Sujin Kang¹, Eunhye Lee¹, Taeyun A. Lee¹, Eun A. Ra¹, Jiseon Lee², Sungwook Lee^2,* & Boyoun Park^1,*¹Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea. ² Immunotherapeutics Branch, Research Institute, National Cancer Center, Goyang 10408, South Korea.

^*Correspondence to Sungwook Lee or Boyoun Park

Abstract

Human cytomegalovirus (HCMV) has evolved sophisticated immune evasion mechanisms that target both the innate and adaptive immune responses. However, how HCMV encoded proteins are involved in this immune escape is not clear. Here, we show that HCMV glycoprotein US9 inhibits the IFN-β response by targeting the mitochondrial antiviral-signaling protein (MAVS) and stimulator of interferon genes (STING)-mediated signaling pathways. US9 accumulation in mitochondria attenuates the mitochondrial membrane potential, leading to promotion of MAVS leakage from the mitochondria. Furthermore, US9 disrupts STING oligomerization and STING?TBK1 association through competitive interaction. Intriguingly, US9 blocks interferon regulatory factor 3 (IRF3) nuclear translocation and its cytoplasmic domain is essential for inhibiting IRF3 activation. Mutant HCMV lacking US7-16 is impaired in antagonism of MAVS/STING-mediated IFN-β expression, an effect that is reversible by the introduction of US9. Our findings indicate that HCMV US9 is an antagonist of IFN signaling to persistently evade host innate antiviral responses.

논문정보

형식Research article
게재일2018년 01월 (BRIC 등록일 2018-01-17)
연구진국내 연구진
분야 생명과학 > 분자생물학

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