title: Japanese encephalitis virus core protein inhibits stress granule formation through an interaction with Caprin-1 and facilitates viral propagation.
abstract: Stress granules (SGs) are cytoplasmic foci composed of stalled translation preinitiation complexes induced by environmental stress stimuli, including viral infection. Since viral propagation completely depends on the host translational machinery, many viruses have evolved to circumvent the induction of SGs or co-opt SG components. In this study, we found that expression of Japanese encephalitis virus (JEV) core protein inhibits SG formation. Caprin-1 was identified as a binding partner of the core protein by an affinity capture mass spectrometry analysis. Alanine scanning mutagenesis revealed that Lys(97) and Arg(98) in the α-helix of the JEV core protein play a crucial role in the interaction with Caprin-1. In cells infected with a mutant JEV in which Lys(97) and Arg(98) were replaced with alanines in the core protein, the inhibition of SG formation was abrogated, and viral propagation was impaired. Furthermore, the mutant JEV exhibited attenuated virulence in mice. These results suggest that the JEV core protein circumvents translational shutoff by inhibiting SG formation through an interaction with Caprin-1 and facilitates viral propagation in vitro and in vivo.
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katoh
authors.forename: Toru
authors.initials: T
authors.lastname: Okamoto
authors.forename: Takasuke
authors.initials: T
authors.lastname: Fukuhara
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kambara
authors.forename: Eiji
authors.initials: E
authors.lastname: Morita
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Mori
authors.forename: Wataru
authors.initials: W
authors.lastname: Kamitani
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Matsuura
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004664:Encephalitis Virus, Japanese / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D011485:Protein Binding; D014758:Viral Core Proteins / Q000378:metabolism*; D014774:Virulence; D014779:Virus Replication
chemical_list: C486562:CAPRIN1 protein, human; D018797:Cell Cycle Proteins; D050505:Mutant Proteins; D014758:Viral Core Proteins