Parisien Jean-Patrick, Bamming Darja, Komuro Akihiko, Ramachandran Aparna, Rodriguez Jason J, Barber Glen, Wojahn Robert D, Horvath Curt M
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
J Virol. 2009 Jul;83(14):7252-60. doi: 10.1128/JVI.00153-09. Epub 2009 Apr 29.
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 approximately 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.
负链RNA病毒副粘病毒科的不同成员通过其V蛋白的作用有效抑制宿主先天免疫反应。V蛋白介导对干扰素调节RNA解旋酶MDA5的干扰，以避免细胞抗病毒反应。对相互作用界面的分析表明，MDA5解旋酶C结构域对于与人副流感病毒2型、副流感病毒5型、麻疹病毒、腮腺炎病毒、亨德拉病毒和尼帕病毒的V蛋白结合是必要且充分的。鉴定出的约130个残基区域在MDA5和相关抗病毒解旋酶LGP2之间高度同源，但与RIG-I不同源。结果表明，副粘病毒V蛋白也可与LGP2结合。发现V蛋白相互作用会破坏由MDA5和LGP2介导的ATP水解。这些发现为V蛋白介导的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蛋白靶向的第二种细胞RNA解旋酶。
