Microbe-induced epigenetic alterations in host cells: the coming era of patho-epigenetics of microbial infections. A review.

摘要

It is well documented that the double-stranded DNA (dsDNA) genomes of certain viruses and the proviral genomes of retroviruses are regularly targeted by epigenetic regulatory mechanisms (DNA methylation, histone modifications, binding of regulatory proteins) in infected cells. In parallel, proteins encoded by viral genomes may affect the activity of a set of cellular promoters by interacting with the very same epigenetic regulatory machinery. This may result in epigenetic dysregulation and subsequent cellular dysfunctions that may manifest in or contribute to the development of pathological changes (e.g. initiation and progression of malignant neoplasms; immunodeficiency). Bacteria infecting mammals may cause diseases in a similar manner, by causing hypermethylation of key cellular promoters at CpG dinucleotides (promoter silencing, e.g. by Campylobacter rectus in the placenta or by Helicobacter pylori in gastric mucosa). I suggest that in addition to viruses and bacteria, other microparasites (protozoa) as well as macroparasites (helminths, arthropods, fungi) may induce pathological changes by epigenetic reprogramming of host cells they are interacting with. Elucidation of the epigenetic consequences of microbe-host interactions (the emerging new field of patho-epigenetics) may have important therapeutic implications because epigenetic processes can be reverted and elimination of microbes inducing patho-epigenetic changes may prevent disease development.