The Pandemic Coronavirus intervenes in the packaging of the DNA and thus prevents the cell from reading out immungs correctly. This is reported by a team around Erica Korb from the University of Pennsylvania based on a detailed analysis of the ORF8 virus protein. According to the publication of the working group in »Nature«, this protein contains a section that corresponds to part of the H3 protein histon protein bound to DNA. This starts a chemical change that should actually take place on H3. If this change is missing, the DNA changes its structure so that important immungs can no longer be read.
Histones are protein complexes around which the DNA strand is wound and play an important role in epigenetics. They ensure that the long strand of genetic material lies in an orderly manner in the cell and does not get tangled. They also determine which DNA segments are openly accessible so that their genes can be read. In order for a gene segment to become accessible, a certain chemical group must be attached to H3 – this is done by the protein KAT2A. Korb's team now suspected that the similarity between ORF8 and H3 causes the chemical reaction to take place on the viral protein instead of where it should actually take place.
In fact, it turned out that this is the case – and even more so. When ORF8 appears in the cell, the concentration of KAT2A decreases significantly. Apparently, the virus protein not only interferes with the chemical reaction itself, but also ensures that the protein necessary for this is broken down. At the same time, chemical changes in the histones that prevent genes from being read increased – the working group therefore considers it possible that ORF8 affects other epigenetic signals. The result is that the DNA is packed more densely and important antiviral genes are read less frequently.
The finding also raises questions about the evolution of SARS coronaviruses as a whole. Because in this virus family, ORF8 is very variable. As studies showed, the protein in the first Sars virus appeared in 2003 did not intervene in the regulation of H3 because it did not have the similar protein section. For this, the motif appears in some SARS relatives in bats. This could indicate that the ability of Sars-Cov-2 to intervene in epigenetics via the histone is an evolutionary innovation, Lisa Thomann and Volker Thiel from the University of Bern write in a comment on the publication.
