Presence and role of cytosine methylation in DNA viruses of animals

Nucleotide composition varies greatly among DNA viruses of animals, yet the evolutionary pressures and biological mechanisms driving these patterns are unclear. One of the most striking discrepancies lies in the frequency of CpG (the dinucleotide CG, linked by a phosphate group), which is underrepresented in most small DNA viruses (those with genomes below 10 kb) but not in larger DNA viruses. Cytosine methylation might be partially responsible, but research on this topic has focused on a few virus groups. For several viruses that integrate their genome into the host genome, the methylation status during this stage has been studied extensively, and the relationship between methylation and viral-induced tumor formation has been examined carefully. However, for actively replicating viruses—particularly small DNA viruses—the methylation status of CpG motifs is rarely known and the effects on the viral life cycle are obscure. In vertebrate host genomes, most cytosines at CpG sites are methylated, which in vertebrates acts to regulate gene expression and facilitates the recognition of unmethylated, potentially pathogen-associated DNA. Here we briefly introduce cytosine methylation before reviewing what is currently known about CpG methylation in DNA viruses.