Epigenetics is the science that explores gene activity, specifically how genes develop in complex organisms and the modifications of gene expression – anything other than mutations or DNA sequence changes.
Studies show a link between epigenetic modifications and a wide array of human diseases, for example, cancer and autoimmune disorders.
One study has examined the connection and the role of various epigenetic players. It highlights their potential uses in the treatment of viral infections, mainly human cytomegalovirus (HCMV) and human immunodeficiency virus (HIV).
- HCMV – Evidence has indicated a strong link between epigenetic alterations and the outcome of HCMV infection.
- HIV – Studies of HIV have focused on two methods to manage viral gene expression or latency. The epigenetic-targeted therapies have shown potential, which could lead to control of the infection and its complexities.
Read the original publication of this study here: [Control of viral infections by epigenetic-targeted therapy]
This study aimed to examine how epigenetic therapy can be used to control or treat viral infections, namely HCMV and HIV.
Control of viral infections by epigenetic-targeted therapy
HIV
Current widespread therapies of HIV are not ideal because of the burden they impose on the patient and the rebound of HIV after cessation. Two new epigenetic therapeutic approaches, namely the “shock and kill” and the “block and lock” strategies, have recently emerged.
Shock and Kill Strategy
HIV can remain hidden and inactive (latent) for months or even years inside particular cells of the immune system. While HIV is in this latent state, the immune system cannot recognize the virus, and current therapies have no effect.
The shock and kill strategy is a two-step process. First, latency-reversing agents are used to reactivate the latent HIV hiding in immune cells (the “shock”). The reactivated cells can then be targeted and killed by the body’s immune system or anti-HIV drugs.
These reversing agents include histone methyltransferase (HMT), histone deacetylase (HDAC), and DNA methyltransferase (DNMT) inhibitors.
Having gained attention after FDA approval for cancer treatment, HDACs, and other inhibitors could be used to reactivate HIV gene expression for treatment.
Block and Lock Strategy
Chemical agents, for example, Tat-inhibiting drug Didehydro-Cortistatin A (dCA), “block” the virus and “lock” the HIV promoter to a super-latent state that is resistant to reactivation.
This strategy is showing so much promise it is emerging as the new treatment to functionally cure HIV.
HCMV
HCMV is a beta-herpes virus, and once infected, the virus remains in your body for life. Yet, most people are unaware they carry HCMV because it is generally asymptomatic in healthy people. The virus is so common it is estimated that 50-80% of all adults in the U.S. have been infected. HCMV infection significantly affects immunocompromised individuals, such as HIV patients. It can result in serious complications in adults and infected babies.
HCMV exhibits two means of viral infection: lytic and latent.
- Lytic – the reproductive stage of the virus.
- Latent – the dormant stage and lifelong presence in the person with the ability to reactivate.
Recent studies have shown that epigenetic modifications play a role in early productive infection events. After viral entry, viral DNA rapidly becomes associated with histones, which makes it a vulnerable candidate to epigenetic modifications.
Using the “shock and kill” method, researchers have determined important sites of HCMV latency. What was previously thought to be a quiescent state is, in reality, a distinctly active process represented by the expression of an amount of latency-associated viral genes.
A solid interaction exists between HCMV latency and epigenetic regulation through alterations of histones and other factors interconnecting directly or indirectly with the genome. Removing the repressive modifications associated with the latent phase can activate the lytic cycle and satisfy lytic gene expression.
Summary
These methods and studies have unveiled new ideas and widened our knowledge about the interaction between viruses, transcription factors, histones, and non-histone-modifying enzymes. Besides infection with HIV and HCMV, any viral infections might be potentially treated by new therapeutics targeting the epigenetic mechanisms. The ability to manipulate this complex system and reverse modifications means we can learn more about an active lytic or latent viral infection. This could lead to permanently silencing the virus by not allowing it to reactivate or by eradicating it after reactivation. Epigenetic-targeted therapy could also illustrate the “two birds, one stone” notion regarding viral co-infection, such as HIV-HCMV.
Takeaways:
- Different strategies have recently emerged that could be used in parallel with other approaches to achieve a fully effective cure for human cytomegalovirus (HCMV) and human immunodeficiency virus (HIV).
- The “shock and kill” and the “block and lock strategy” are examples of these new epigenetic therapeutic approaches for HIV.
- These new methods might potentially treat any viral infections.
- As a pioneering research area, epigenetic manipulations could further develop broad-spectrum antivirals and a possible cure for human viral infections.
You can read the original publication of this study here: [Control of viral infections by epigenetic-targeted therapy]
