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 doubl...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 hC and reovirus. The HELICc domain of DHX33 was shown to bind poly hC. 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 to MAVS and VISA）. The inhibition of DHX33 expression by RNA interference blocked the poly hC-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.展开更多
文摘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 hC and reovirus. The HELICc domain of DHX33 was shown to bind poly hC. 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 to MAVS and VISA）. The inhibition of DHX33 expression by RNA interference blocked the poly hC-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.
