title: Japanese encephalitis virus NS1' protein depends on pseudoknot secondary structure and is cleaved by caspase during virus infection and cell apoptosis.
abstract: Japanese encephalitis virus (JEV) is a flavivirus with a complex life cycle involving mosquito vectors that mainly target birds and pigs, and causes severe encephalitis in children in Asia. Neurotropic flaviviruses of the JEV serogroup have a particular characteristic of expressing a unique nonstructural NS1' protein, which is a prolongation of NS1 at the C terminus by 52 amino acids derived from a pseudoknot-driven-1 translation frameshift. Protein NS1' is associated with virus neuro-invasiveness. In this study, the need of the pseudoknot structure for NS1' synthesis was confirmed. By using a specific antibody against the prolonged peptide, NS1' was found to be absent from the JEV SA14-14-2 vaccine strain, resulting from a single nucleotide silent mutation in the pseudoknot. A partial cleavage of NS1' at a specific site of its C-terminal appendix recognized by caspases and inhibited by caspase inhibitors suggests a unique feature of intracellular NS1'.
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Yu
authors.forename: Vincent
authors.initials: V
authors.lastname: Deubel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004672:Encephalitis, Japanese / Q000378:metabolism* / Q000821:virology; D051379:Mice; D009154:Mutation; D017433:Protein Structure, Secondary; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014765:Viral Vaccines / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D061945:Caspase Inhibitors; C100315:NS1 protein, Flavivirus; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines; D020169:Caspases