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KMID : 1034820190150040425
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Molecular & Cellular Toxicology
2019 Volume.15 No. 4 p.425 ~ p.430
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Specific elimination of coxsackievirus B3 infected cells with a protein engineered toxin-antitoxin system
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Park Jung-Ho
Park Jin-Ho
Choi Won-Ho
Lim Byung-Kwan
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Abstract
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Backgrounds: Coxsackievirus B3 (CVB3) is a member of the family Picornaviridae, and along with polio-viruses, belongs to the Enterovirus genus. The CVB3 genome is composed single-stranded RNA encoding polyproteins, which are cleaved to individual functional proteins by 2A and 3C proteases proteins which have been targeted for drug development. Here, we showed that protease activity required to activate a toxic protein may be used to prevent viral infection.
Methods: We modified the MazE-MazF antitoxin-toxin system of Escherichia coli to fuse a C-terminal fragment of MazE to the N-terminal end of toxin MazF with a linker having a specific protease cleavage site for CVB3. This fusion protein formed a stable dimer and was capable of inactivating the mRNA interferase activity of MazF which cleaves the ACA sequence in mRNA substrates.
Results: The incubation of 2A proteases with the fusion proteins induced cleavage between the MazE and MazF fragments from the fusion proteins; the subsequent release of MazF significantly inhibited virus replication. Additionally, we note that, CVB3 infected HeLa cells quickly died through a MazF toxin mediated effect before virus protein expression.
Conclusion: These findings suggest that the MazEF fusion protein has a strong potential to be developed as an anti-virus therapy following CVB3 infection.
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KEYWORD
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Coxsackievirus, MazEF, Antitoxin, Cardiotropic, Polyprotein, Proteases
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