Viral control of the epitranscriptome: alphaherpesvirus-induced m6A mRNA demethylation

Alphaherpesviruses are extremely successful viral pathogens and have developed several
mechanisms to take control of the host cells that they infect. We have exciting evidence that these
viruses take firm control over a host cell system that regulates the production of proteins, the
epitranscriptome. The genetic information of a host is present in its DNA, e.g. the genes. Specific
genes give rise to the production of specific proteins, via intermediate molecules termed mRNA.
Different proteins all have their particular functions, and their expression needs to be carefully
regulated. One mechanism to control protein expression that we are just beginning to understand is
the epitranscriptome. The epitranscriptome consists of different chemical modifications in the
mRNA intermediate molecules that affect different properties of the mRNA (e.g. transport &
stability) and thereby profoundly affect protein expression. The most abundant of these mRNA
modifications is m6A methylation. We have recently discovered that alphaherpesviruses very
efficiently shut down the m6A mRNA methylation program and trigger degradation of a protein that
is crucial for m6A mRNA methylation. We have indications that this contributes to efficient virus
replication, and thus represents a new viral mechanism to take control over the host cell. We will
investigate the causes and consequences of alphaherpesvirus-induced m6A demethylation, and
whether these viruses also affect other types of mRNA methylation.