The role of Herpes Virus promoter methylation in the realization of pathogenic potential in the example of Marek’s Disease

Abstract

Marek’s disease virus is ubiquitous and can harm not only poultry, but also be oncogenic for humans. VBM and malignant tumors induced by them are a convenient and accessible natural model for studying herpesvirus-associated carcinogenesis. To date, according to our observations, there are additional risks of human infection with the Marek’s disease virus - the disease began to appear in broiler chickens 30 days and older, i.e. contact with poultry meat carries a risk of infection. In addition, COVID-19 disease may be accompanied by folic acid deficiency, i.e. a violation of the folate cycle in humans, which increases the risk of manifestation of diseases associated with DNA viruses, since a violation of the folate cycle can reduce the activity of DNA methylation, incl. viral DNA. Methylation is carried out enzymatically in the first minutes after DNA replication, i.e. postreplicatively. Since the DNA nucleotide sequence does not change, methylation is essentially an epigenetic event. We have studied the relationship between the methylation of promoters of the Marek’s disease virus and the copy number of the virus. The assessment of the presence or absence of methylation, as well as partial methylation, was carried out on the basis of identifying the difference between the threshold cycles dC(t). The presence of unmethylated sites included in the studied promoter sequence was detected on the basis of the ability of methylsensitive restrictases AciI and GlaI. A correlation was found between the concentration of genomic DNA of the Marek’s disease virus serotype 1 strain CVI 988 in cell culture and the presence of demethylated CpG islands in the composition of promoters located at position 9413-9865 bp. and 127943 - 128193 b.p. genomic DNA of the virus. The data obtained make it possible to explain the mechanism of the increase in the pathogenicity of herpesvirus infections under conditions of a decrease in the activity of viral DNA methylation in the body.

Assessment of the Epidemic Potential of the Marek’s Disease Virus in the Russian Federation

“…Infection of broiler chickens with the Marek's disease virus of birds unfavorable for this disease was assessed by the results of PCR testing by the generally accepted method [16].…”