The interaction between the helicase DHX33 and IPS-1 as a novel pathway to sense double-stranded RNA and RNA viruses in myeloid dendritic cells.

The interaction between the helicase DHX33 and IPS-1 as a novel pathway to sense double-stranded RNA and RNA viruses in myeloid dendritic cells.
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DOI:
10.1038/cmi.2013.40
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发表时间:
2014-01
影响因子:
24.1
通讯作者:
--
中科院分区:
医学1区
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--
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在真核生物中,至少有60个DExD/H解旋酶家族成员,其中许多成员能够感知病毒核酸。通过对所有已知家族成员的筛选,我们确定解旋酶DHX33是髓系树突状细胞(MDCs)中的一种新的双链RNA(DsRNA)传感器。利用小分子异源双链RNA(ShRNA)敲除DHX33基因,可阻断MDCS对Poly I:C和呼肠孤病毒产生I型干扰素的能力。DHX33的HELICc结构域与Poly I:C结合,DHX33与IPS-1之间的相互作用由DHX33的HELICc区域和IPS-1的C末端结构域(又称MAVS和VISA)介导。RNA干扰抑制DHX33的表达可阻断Poly I:C诱导的MAP激酶、NF-κB和IRF3的激活。解旋酶DHX33与IPS-1之间的相互作用不依赖于RIG-I/MDA5,可能是在MDCS中检测Poly I:C和RNA病毒的一条新途径。
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 to MAVS and VISA). The inhibition of DHX33 expression by RNA interference blocked the poly I:C-induced activation of MAP kinases, NF-κB 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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