Challenges for the production of virus-like particles in insect cells: The case of rotavirus-like particles

Virus-like particles (VLP) are formed when viral structural proteins are produced in an heterologous expression system. Such proteins assemble into structures that are morphologically similar to native viruses but lack the viral genome. VLP are complex structures with a wide variety of applications, ranging from basic research and vaccines to potential new uses in nanotechnology. Production of VLP is a challenging task, as both the synthesis and assembly of one or more recombinant proteins are required. This is the case for VLP of rotavirus (RLP), which is an RNA virus with a capsid formed by 1860 monomers of four different proteins. In addition, the production of most VLP requires the simultaneous expression and assembly of several recombinant proteins, which – for the case of RLP – needs to occur in a single host cell. The insect cell baculovirus expression vector system (IC-BEVS) has been shown to be a powerful and convenient system for rapidly and easily producing VLP, due to several convenient features, including its versatility and the short time needed for construction of recombinant baculovirus. In this review, the specific case of rotavirus-like particle (RLP) production by the IC-BEVS is discussed, with emphasis on bioprocess engineering issues that exist and their solutions. Many culture strategies discussed here can be useful for the production of other VLP.