期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 11, 期 1, 页码 49-57出版社
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/cmi.2013.40
关键词
DHX33; helicase; innate immunity; IPS-1; myeloid dendritic cell; viral nucleic acid
类别
资金
- NIAID NIH HHS [R37 AI091947] Funding Source: Medline
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R37AI091947] Funding Source: NIH RePORTER
In eukaryotes, there are at least 60 members of the DExD/H helicase family, many of which are able to sense viral nucleic acids. By screening all known family members, we identified the helicase DHX33 as a novel double-stranded RNA (dsRNA) sensor in myeloid dendritic cells (mDCs). The knockdown of DHX33 using small heteroduplex RNA (shRNA) blocked the ability of mDCs to produce type I interferon (IFN) in response to poly I: C and reovirus. The HELICc domain of DHX33 was shown to bind poly I: C. The interaction between DHX33 and IPS-1 is mediated by the HELICc region of DHX33 and the C-terminal domain of IPS-1 (also referred toMAVS and VISA). The inhibition of DHX33 expression byRNA interference blocked the poly I: C-induced activation of MAP kinases, NF-kB and IRF3. The interaction between the helicase DHX33 and IPS-1 was independent of RIG-I/MDA5 and may be a novel pathway for sensing poly I: C and RNA viruses in mDCs.
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