Host epigenetic modifications by oncogenic viruses

Abstract

Epigenetic alterations represent an important step in the initiation and progression of most human cancers, but it is difficult to differentiate the early cancer causing alterations from later consequences. Oncogenic viruses can induce transformation via expression of only a small number of viral genes. Therefore, the mechanisms by which oncogenic viruses cause cancer may provide clues as to which epigenetic alterations are critical in early carcinogenesis.

Figure 1

Viral control of the host epigenome. Epigenetic control of gene expression occurs at four different levels starting with chromatin packaging into higher order chromatin structures controlled by ATP-dependent chromatin remodelling complexes (ATP-DRs), PcG and TxG genes. DNA is wrapped around nucleosomes that are assembled from dimers of the histones H2A, H2B, H3 and H4, all of which contain tails that can be either acetylated (HATs) and demethylated (HDMTs) during active transcription or deactylated (HDACs) and highly methylated (HMTs) during repressed transcription. At the nucleotide level, epigenetic control via DNA methylation is mediated by the DNA methylating enzymes (DNMTs), methyl-DNA-binding proteins (e.g. MeCBPs) and cytosine deaminases that could act as demethylating enzymes. Finally, transcriptional repression is also mediated by microRNAs. Oncogenic viruses target DNA methyltransferase activity and p300/CBP histone acetyltransferase activity, but may also target other epigenetic mechanisms to induce carcinogenesis.