Dear Clarence Hu

EBV seems to employ epigenetic mechanisms to control the host transcriptome and to control expression of its own virally encoded genes. Upon initial infection of a cell, the unmethylated viral genome can undergo viral replication with new virion production, while a subset of infected cells acquires a highly methylated viral genome that squelches expression of foreign proteins and mediates long-term viral persistence by way of latent infection. Infected tumors tend to have highly methylated EBV DNA, and methylation-related silencing of viral genes helps explain how infected tumors evade immune destruction.

The reagents mentioned by you like 5-aza-deoxycytidine (5-aza), Sodium butyrate, Tetracycline derivative doxycycline (Dox), etc. are demethylating agents with the capacity to induce transient DNA hypomethylation.

Deliberate attempt to reduce the DNA methylation in EBV-associated cancer with the aim to activate the expression of cellular and viral genes has the potential to achieve two potentially therapeutic events.

First, it may result in reactivation of the expression of viral genes that expose the cells to attack by the immune system (the recognition of the target by virus-specific cytotoxic T-cells).

Secondly, it may result in the expression of important cellular genes that cause the cancer cells to stop proliferating or to die through apoptosis.

So, deliberate attempt to alter DNA methylation presents an attractive research direction which may lead to new therapeutic approaches to treat EBV-associated cancer.

In a way, yes, it is specific to EBV because EBV employs epigenetic mechanisms namely, attains a highly methylated viral genome that helps mediate long-term viral persistence by way of latent infection evading the immune system. When demethylating agents are used, they reactivate viral gene expression and as a result are easily recognized and attacked by the immune system.

I have attached a research article for your reference.

https://www.frontiersin.org/articles/10.3389/fcimb.2021.695093/full

Best Wishes.