The majority of new and emerging pathogens of humans and animals are RNA viruses. Although their genomes are typically very short (<10,000 bases) and encoded few genes and have, at least conceptually, a simple replication cycle, their continued existence requires an ability to evade sophisticated and powerful interferon-coupled cellular defences and systemic inflammatory and adaptive immune responses. In addition to encoding a sophisticated range of cellular defence evasion factors, their highly compact RNA virus genomes possess many compositional and structural attributes in addition to their roles in encoding viral proteins. For example, genomes of single stranded RNA viruses may possess genome-scale ordered RNA structure (GORS), a property in mammalian viruses that specifically associated with an ability to establish persistent infections in their natural hots. However, structured genomes are found among many groups of arthropod and plant viruses suggesting that this property lays a much deeper role in interaction between virus and cellular defence mechanisms.

Most classes of RNA viruses infecting vertebrates and plants suppress of CpG and UpA dinucleotide frequencies, independently of host methylation-linked loss of CpGs in host DNA genomes. We are currently experimentally investigating the cellular pathways that recognise this compositional attribute and the mechanisms by which insertion of additional CpG and UpA dinucleotides into their genomes profoundly attenuates their replication. We have also discovered that reduction of CpG/UpA dinucleotide frequencies in a wide range of virus genomes below those found in nature accelerates their replication both in vitro and in vivo. These findings have a major potential for enhancing production of inactivated viral vaccines (eg. poliovirus, IAV), and expression of vector reporter genes and transgenes in wider areas of biotechnology. More fundamentally, the findings introduce a new evolutionary paradigm where dinucleotide composition of viral genomes is subjected to selection pressures independently of coding capacity and profoundly influences host/pathogen interactions.