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Cleavage of eukaryotic initiation factor eIF5B by enterovirus 3C proteases
Sylvain de Breyne1, Jennifer M Bonderoff, Konstantin M Chumakov
1Department of Microbiology and Immunology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA.
Virology
|June 24, 2008
Summary
Enteroviruses like poliovirus cleave eukaryotic initiation factor 5B (eIF5B), a key translation regulator. This cleavage contributes to the shutdown of host cell translation during viral infection.
Area of Science:
- Molecular Biology
- Virology
- Biochemistry
Background:
- Enteroviruses, including poliovirus (PV), Coxsackie B virus (CVB), and rhinovirus (HRV), are known to inhibit host cell translation early in infection.
- While enterovirus translation initially predominates, it is eventually shut off, suggesting a complex regulatory mechanism.
Purpose of the Study:
- To investigate the role of eukaryotic initiation factor 5B (eIF5B) in enterovirus-induced translation shutoff.
- To determine if viral proteases are responsible for eIF5B cleavage during infection.
Main Methods:
- Proteolytic cleavage of eIF5B was assessed in cultured cells infected with PV and CVB.
- Recombinant enterovirus 3C proteases (3Cpro) were used to cleave purified rabbit eIF5B in vitro.
- The cleavage site on eIF5B was identified and characterized.
Main Results:
- Proteolytic cleavage of eIF5B was observed in cultured cells infected with PV and CVB, starting at 3 hours post-infection.
- Recombinant PV, CVB, and HRV 3Cpro efficiently cleaved purified eIF5B in vitro at a specific site (VVEQG).
- Cleavage by 3Cpro separates the N-terminal domain from the essential GTPase and C-terminal domains of eIF5B.
Conclusions:
- Enterovirus 3C proteases cleave eukaryotic initiation factor 5B (eIF5B).
- This 3Cpro-mediated cleavage of eIF5B likely plays an accessory role in the shutoff of host cell translation during enterovirus infections.
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