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HCMV-encoded US7 and US8 act as antagonists of innate immunity by distinctively targeting TLR-signaling pathways.

Authors
 Areum Park  ;  Eun A. Ra  ;  Taeyun A. Lee  ;  Hyun jin Choi  ;  Eunhye Lee  ;  1 Sujin Kang  ;  Jun-Young Seo  ;  Sungwook Lee  ;  and Boyoun Park 
Citation
 NATURE COMMUNICATIONS, Vol.10(1) : 4670, 2019 
Journal Title
NATURE COMMUNICATIONS
Issue Date
2019
Abstract
The mechanisms by which many human cytomegalovirus (HCMV)-encoded proteins help the virus to evade immune surveillance remain poorly understood. In particular, it is unknown whether HCMV proteins arrest Toll-like receptor (TLR) signaling pathways required for antiviral defense. Here, we report that US7 and US8 as key suppressors that bind both TLR3 and TLR4, facilitating their destabilization by distinct mechanisms. US7 exploits the ER-associated degradation components Derlin-1 and Sec61, promoting ubiquitination of TLR3 and TLR4. US8 not only disrupts the TLR3-UNC93B1 association but also targets TLR4 to the lysosome, resulting in rapid degradation of the TLR. Accordingly, a mutant HCMV lacking the US7-US16 region has an impaired ability to hinder TLR3 and TLR4 activation, and the impairment is reversed by the introduction of US7 or US8. Our findings reveal an inhibitory effect of HCMV on TLR signaling, which contributes to persistent avoidance of the host antiviral response to achieve viral latency.
Files in This Item:
T201903841.pdf Download
DOI
10.1038/s41467-019-12641-4
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Seo, Jun Young(서준영) ORCID logo https://orcid.org/0000-0003-4004-2013
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/173058
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