Journal
NATURE COMMUNICATIONS
Volume 4, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms2857
Keywords
-
Categories
Funding
- Ministry of Education, Science, and Culture
- Ministry of Health, Labor, and Welfare of Japan
- Akiyama Life Science Foundation
- Grants-in-Aid for Scientific Research [23590558] Funding Source: KAKEN
Ask authors/readers for more resources
Endosomal Toll-like receptor 3 (TLR3) serves as a sensor of viral infection and sterile tissue necrosis. Although TLR3 recognizes double-stranded RNA, little is known about structural features of virus- or host-derived RNAs that activate TLR3 in infection/inflammatory states. Here we demonstrate that poliovirus-derived single-stranded RNA segments harbouring stem structures with bulge/internal loops are potent TLR3 agonists. Functional poliovirus-RNAs are resistant to degradation and efficiently induce interferon-alpha/beta and proinflammatory cytokines in human and mouse cells in a TLR3-dependent manner. The N- and C-terminal double-stranded RNA-binding sites of TLR3 are required for poliovirus-RNA-mediated TLR3 activation. Like polyriboinosinic:polyribocytidylic acid, a synthetic double-stranded RNA, these RNAs are internalized into cells via raftlin-mediated endocytosis and colocalized with TLR3. Raftlin-associated RNA uptake machinery and the TLR3 RNA-sensing system appear to recognize an appropriate topology of multiple RNA duplexes in poliovirus-RNAs. Hence, TLR3 is a sensor of extracellular viral/host RNA with stable stem structures derived from infection or inflammation-damaged cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available