Coding Biases and Viral Fitness

Codon usage bias has also been described for DNA and RNA viruses. Among the latter, poliovirus (PV) has selected through a codon bias similar to that of its human host species (“optimized”), while the codon bias of hepatitis A virus (HAV) is very different from that of its host (“deoptimized”). Picornavirus internal ribosome entry site (IRES) types have probably evolved by gradual addition of domains and elements that improved their function in ribosome recruitment or otherwise conferred regulation to the process of viral protein synthesis in a specific cell environment. The highly inefficient IRES combined with the lack of a mechanism to induce cellular shutoff leads in HAV to an unfair competition for the cellular translational machinery. An intriguing connection exists between codon bias, codon pair bias, and dinucleotide bias in mammalian genomes. Viral genomes, especially of RNA viruses and retroviruses, are short enough to make them amenable to whole-genome synthesis with currently available technology. Such freedom of design can provide tremendous power to reengineer DNA- and RNA-coding sequences at will to study the impact on viral fitness of large-scale changes in codon bias, codon pair bias, dinucleotide biases, GC content, RNA secondary structures, and other sequence signatures, with the aim to develop a new platform for vaccine design and genetic engineering. The codon usage selected through evolution by PV, HAV and its contribution to their in vivo fitness are still not completely elucidated, but it is certainly remarkable how they follow clearly different strategies.