Minárovits J
Microbiological Research Group, National Center for Epidemiology, Piheno u. 1, H-1529 Budapest, Hungary.
Acta Microbiol Immunol Hung. 2009 Mar;56(1):1-19. doi: 10.1556/AMicr.56.2009.1.1.
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.
有充分的文献记载，某些病毒的双链DNA（dsDNA）基因组和逆转录病毒的前病毒基因组在受感染细胞中经常受到表观遗传调控机制（DNA甲基化、组蛋白修饰、调节蛋白结合）的靶向作用。与此同时，病毒基因组编码的蛋白质可能通过与相同的表观遗传调控机制相互作用，影响一组细胞启动子的活性。这可能导致表观遗传失调以及随后的细胞功能障碍，这些功能障碍可能表现为病理变化或促成病理变化的发展（例如恶性肿瘤的发生和进展；免疫缺陷）。感染哺乳动物的细菌可能以类似的方式引起疾病，通过导致关键细胞启动子在CpG二核苷酸处发生高甲基化（启动子沉默，例如胎盘内的直肠弯曲杆菌或胃黏膜内的幽门螺杆菌）。我认为，除了病毒和细菌之外，其他微寄生虫（原生动物）以及大寄生虫（蠕虫、节肢动物、真菌）也可能通过对与其相互作用的宿主细胞进行表观遗传重编程来诱导病理变化。阐明微生物与宿主相互作用的表观遗传后果（新兴的病理表观遗传学新领域）可能具有重要的治疗意义，因为表观遗传过程可以逆转，消除诱导病理表观遗传变化的微生物可能预防疾病的发展。
