Analysis of the mechanism of translation initiation complex formation on feline calicivirus mRNA

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When viruses infect cells they need to utilise the host cell's protein synthesis machinery to synthesise new viral proteins. Viruses have therefore evolved a number of novel ways to ensure translation (or decoding) of their messenger RNAs (mRNAs) into protein in order to compete with cellular mRNAs. Members of the calicivirus family are responsible for important diseases of man and animals; noroviruses cause gastroenteritis or 'projectile vomiting' in humans and outbreaks are often seen in hospitals, cruise ships and in military camps, while feline calicivirus (FCV) causes cat 'flu. Currently, little is known about what happens when these viruses infect cells, and how new virus particles are made. We have shown that a viral protein attached to the end of the viral mRNAs (VPg) binds to a key cellular protein synthesis factor, eIF4E. This factor usually binds to a structure on cellular mRNAs (termed the 'cap') and helps recruit the protein synthesis machinery (including the ribosome). This suggests that caliciviruses utilise a novel mechanism to recruit ribosomes to their mRNAs, with VPg acting as a 'cap substitute'. We have also demonstrated that other cellular proteins bind to the FCV mRNA itself and may help to recruit ribosomes. We now aim to define further these interactions and the roles they play in virus protein synthesis and replication. This will aid in the development of novel antiviral therapies for this important group of viruses.