Rotavirus protein NSP3 shuts off host cell protein synthesis.
A recombinant vaccinia virus encoding rotavirus protein NSP3 driven by an internal ribosome entry site (IRES) from the encephalomyocarditis (EMC) virus was able to abate protein synthesis in BSC1 cells by 25-fold, with as much as 30% of the remaining protein synthesis being NSP3. Hence NSP3 shuts off host cell protein synthesis down to the level seen during rotavirus infection but is unable to prevent translation from EMC IRES-driven genes. This effect was abolished by deletions in the eIF4G-binding (aa 274-313) and the dimerization (aa 150-206) but not the viral mRNA-binding (aa 83-149) domains, supporting that NSP3 functions in vivo as a dimer. Binding of eIF4G by NSP3 has been implicated in interfering with mRNA 5'-3' circularization, hence such circularization is essential for translation in mammalian cells.
Padilla-Noriega
Luis
L
Departamento de Biología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70-228, Mexico City 04510, Mexico. lpadilla@servidor.unam.mx
Paniagua
Octavio
O
Guzmán-León
Simón
S
D000818:Animals; D002460:Cell Line; D019281:Dimerization; D004686:Encephalomyocarditis virus / Q000472:pathogenicity / Q000502:physiology*; D039603:Eukaryotic Initiation Factor-4G; D017353:Gene Deletion; D006801:Humans; D010448:Peptide Initiation Factors / Q000737:chemistry / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D017361:Viral Nonstructural Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics
D039603:Eukaryotic Initiation Factor-4G; C082740:NSP3 protein, Rotavirus; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins