A Shared Interface Mediates Paramyxovirus Interference with Antiviral RNA Helicases MDA5 and LGP2
A Shared Interface Mediates Paramyxovirus Interference with Antiviral RNA Helicases MDA5 and LGP2
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DOI：
10.1128/jvi.00153-09
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发表时间：
2009-07-15
影响因子：
5.4
通讯作者：
Horvath, Curt M.
中科院分区：
文献类型：
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作者：
Parisien, Jean-Patrick;Bamming, Darja;Horvath, Curt M.
负链RNA病毒副粘病毒家族的不同成员通过其V蛋白的作用有效地抑制宿主先天免疫反应。V蛋白介导干扰素调节RNA解旋酶MDA5的干扰，以避免细胞抗病毒反应。相互作用界面分析显示，MDA5解旋酶C结构域是与人2型副流感病毒、5型副流感病毒、麻疹病毒、腮腺炎病毒、亨德拉病毒和尼帕病毒的V蛋白结合所必需和充分的。MDA5与相关抗病毒解旋酶LGP2高度同源，而与rig - 1高度同源。结果表明副粘病毒V蛋白也能与LGP2结合。发现V蛋白相互作用破坏了MDA5和LGP2介导的ATP水解。这些发现为V蛋白介导解旋酶干扰提供了潜在的机制基础，并确定LGP2是副粘病毒V蛋白靶向的第二个细胞RNA解旋酶。
Diverse members of the Paramyxovirus family of negative-strand RNA viruses effectively suppress host innate immune responses through the actions of their V proteins. The V protein mediates interference with the interferon regulatory RNA helicase MDA5 to avoid cellular antiviral responses. Analysis of the interaction interface revealed the MDA5 helicase C domain as necessary and sufficient for association with V proteins from human parainfluenza virus type 2, parainfluenza virus type 5, measles virus, mumps virus, Hendra virus, and Nipah virus. The identified similar to 130-residue region is highly homologous between MDA5 and the related antiviral helicase LGP2, but not RIG-I. Results indicate that the paramyxovirus V proteins can also associate with LGP2. The V protein interaction was found to disrupt ATP hydrolysis mediated by both MDA5 and LGP2. These findings provide a potential mechanistic basis for V protein-mediated helicase interference and identify LGP2 as a second cellular RNA helicase targeted by paramyxovirus V proteins.