Tiia Koho

University of Tampere
Supervisor: Markku S. Kulomaa, Vesa Hytönen
Funding: other
Date: 1/11/2007

Structural and functional studies on recombinant and genetically engineered virus-like particles

Virus-like particles (VLPs) are formed by the self-assembly of envelope and/or capsid proteins of the virus. In many cases such VLPs have the structural characteristics and antigenicity similar to the parental virus. Some VLPs have already proven successful as vaccines. In other cases, the structural components of VLPs are suitable to the insertion or fusion of foreign sequences, allowing the production of genetically modified VLPs. VLPs can also be exploited as carriers for foreign molecules via chemical conjugation. In my study VLPs are derived from two human non-enveloped, single stranded RNA viruses. VLPs are non-infectious since they do not contain genetic material.

Early insights into self-assembly/disassembly and packaging mechanisms have been proposed by several physical, structural and molecular experiments. From these investigations, it can be concluded that VLP self-assembly involves a variety of hydrophobic, electrostatic and covalent interactions. Although self-assembly is often spontaneous under favourable conditions, there is also evidence that certain scaffold proteins are required as catalyst for some viral proteins to assemble in biological systems. Hence, self-assembly is a multimolecular dynamic reaction in which unimolecular protein folding is involved, but it might not be the sole determinant. Solving the mechanisms involved in self-assembling is still a challenge.

Virus capsids are relatively simple; they are typically formed from multiple copies of limited number of different proteins and therefore provide information regarding the principles of chemical self-assembly. The aims of my study are, firstly, to express VLPs from isolated virus genomes and to learn about the structures that contribute the self-assembly, stability and receptor activating capacity of the VLPs, and, secondly, to functionalize and manipulate VLPs via protein engineering.