Cleavage of eukaryotic initiation factor eIF5B by enterovirus 3C proteases.
The enteroviruses poliovirus (PV), Coxsackie B virus (CVB) and rhinovirus (HRV) are members of Picornaviridae that inhibit host cell translation early in infection. Enterovirus translation soon predominates in infected cells, but eventually also shuts off. This complex pattern of modulation of translation suggests regulation by a multifactorial mechanism. We report here that eIF5B is proteolytically cleaved during PV and CVB infection of cultured cells, beginning at 3 hours post-infection and increasing thereafter. Recombinant PV, CVB and HRV 3Cpro cleaved purified native rabbit eukaryotic initiation factor (eIF) 5B in vitro at a single site (VVEQG, equivalent to VMEQG479 in human eIF5B) that is consistent with the cleavage specificity of enterovirus 3C proteases. Cleavage separates the N-terminal domain of eIF5B from its essential conserved central GTPase and C-terminal domains. 3Cpro-mediated cleavage of eIF5B may thus play an accessory role in the shutoff of translation that occurs in enterovirus-infected cells.
Department of Microbiology and Immunology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA.
Sylvain
S
de Breyne
Jennifer M
JM
Bonderoff
Konstantin M
KM
Chumakov
Richard E
RE
Lloyd
Christopher U T
CU
Hellen
D000086042:3C Viral Proteases; D000818:Animals; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism* / Q000494:pharmacology; D004770:Enterovirus / Q000201:enzymology / Q000472:pathogenicity; D029822:Enterovirus B, Human / Q000201:enzymology* / Q000472:pathogenicity; D039642:Eukaryotic Initiation Factors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D017955:Poliovirus / Q000201:enzymology* / Q000472:pathogenicity; D014176:Protein Biosynthesis / Q000187:drug effects; D011817:Rabbits; D012229:Rhinovirus / Q000201:enzymology / Q000472:pathogenicity; D014764:Viral Proteins / Q000378:metabolism* / Q000494:pharmacology
D039642:Eukaryotic Initiation Factors; D014764:Viral Proteins; C451459:eukaryotic initiation factor-5B; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases