Abstract
Virus-like particles (VLPs) are formed by the self-assembly of envelope and/or capsid proteins from many viruses. Some VLPs have been proven successful as vaccines, and others have recently found applications as carriers for foreign antigens or as scaffolds in nanoparticle biotechnology. However, production of VLP was usually impeded due to low water-solubility of recombinant virus capsid proteins. Previous studies revealed that virus capsid and envelope proteins were often posttranslationally modified by SUMO in vivo, leading into a hypothesis that SUMO modification might be a common mechanism for virus proteins to retain water-solubility or prevent improper self-aggregation before virus assembly. We then propose a simple approach to produce VLPs of viruses, e.g., foot-and-mouth disease virus (FMDV). An improved SUMO fusion protein system we developed recently was applied to the simultaneous expression of three capsid proteins of FMDV in E. coli. The three SUMO fusion proteins formed a stable heterotrimeric complex. Proteolytic removal of SUMO moieties from the ternary complexes resulted in VLPs with size and shape resembling the authentic FMDV. The method described here can also apply to produce capsid/envelope protein complexes or VLPs of other disease-causing viruses.
Highlights
Foot-and-mouth disease (FMD) is a severe, highly contagious viral disease of cloven-hoofed animals, such as cattle, pig, sheep, goats and deer, and is the most economically devastating livestock disease in the world
Animals can be protected against FMD by vaccination with killed foot-and-mouth disease virus (FMDV), prophylactic vaccination is still impossible for several reasons
Attempts have been made to produce subunit vaccines by expressing FMDV capsid protein(s) in E. coli. These recombinant capsid proteins exhibited poor water solubility and were administered in vaccine studies either in denatured forms [5,6,7] or after a tedious refolding procedure [8]. To overcome this technical bottleneck, we recently developed an improved SUMO (Smt3) fusion protein system in E. coli to produce several water-soluble virus capsid proteins, including FMDV-VP3 [9]
Summary
Foot-and-mouth disease (FMD) is a severe, highly contagious viral disease of cloven-hoofed animals, such as cattle, pig, sheep, goats and deer, and is the most economically devastating livestock disease in the world. Animals can be protected against FMD by vaccination with killed FMDV, prophylactic vaccination is still impossible for several reasons. The risks of new outbreaks are increasing due to globalization and the increased possibility of bioterrorism. If it were introduced into the United States, which is FMD-free, the disease could cause 100 billions of dollars in losses to the U.S economy [1]. The development of a cheap and noninfectious subunit or virus-like particle (VLP) vaccine for prophylactic use is a matter of world-wide interest. VLPs consist of protein(s) derived from the capsid of a virus They are noninfectious because while they resemble the virus from which they were derived, they lack the viral (page number not for citation purposes)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
