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

当病毒感染细胞时，它们需要利用宿主细胞的蛋白质合成机制来合成新的病毒蛋白质。因此，病毒进化出了许多新的方法来确保它们的信使rna （mrna）翻译（或解码）成蛋白质，以便与细胞mrna竞争。杯状病毒家族的成员对人类和动物的重要疾病负有责任；诺如病毒引起人类肠胃炎或“抛射性呕吐”，经常在医院、游轮和军营中爆发，而猫杯状病毒（FCV）引起猫流感。目前，人们对这些病毒感染细胞时会发生什么以及如何制造新的病毒颗粒知之甚少。我们已经证明，附着在病毒mrna末端的病毒蛋白（VPg）与关键的细胞蛋白合成因子eIF4E结合。该因子通常与细胞mrna上的结构（称为“帽”）结合，并帮助招募蛋白质合成机器（包括核糖体）。这表明杯状病毒利用一种新机制将核糖体招募到它们的mrna上，VPg充当“帽代物”。我们还证明了其他细胞蛋白与FCV mRNA本身结合，并可能有助于招募核糖体。我们现在的目标是进一步确定这些相互作用及其在病毒蛋白合成和复制中所起的作用。这将有助于开发针对这类重要病毒的新型抗病毒疗法。

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.