A shared interface mediates paramyxovirus interference with antiviral RNA helicases MDA5 and LGP2.
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.
Parisien
Jean-Patrick
JP
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
Bamming
Darja
D
Komuro
Akihiko
A
Ramachandran
Aparna
A
Rodriguez
Jason J
JJ
Barber
Glen
G
Wojahn
Robert D
RD
Horvath
Curt M
CM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000998:Antiviral Agents; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D018184:Paramyxoviridae Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D018098:Paramyxovirinae / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D014762:Viral Interference; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D000998:Antiviral Agents; C437968:PLAAT4 protein, human; D018168:Receptors, Retinoic Acid; D014764:Viral Proteins; D000255:Adenosine Triphosphate; C520569:DHX58 protein, human; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases