Emerging viral infections pose a major threat to global public health. In the last two decades, the world has dealt with several fatal outbreaks from the Swine Flu to Ebola to Zika infections and more. The latest to appear is COVID-19, which emerged in December in Wuhan, China and spread quickly around the globe. Although this disease is new, the virus itself is not entirely unknown. It’s actually a type of coronavirus (CoV) –one that is similar to SARS-CoV and MERS-CoV, all which attack the respiratory system and derive from animal origin.
Information about COVID-19 (also referred to as nCov-19) is currently still evolving, and health officials don’t know for certain the true severity of the disease. However, researchers have investigated comparable pathogens in the past and have found similar mechanisms may be involved in the development of these types of infections. Perhaps the data from these studies could be useful in shedding light on how new viruses, like COVID-19, are able to spread and mutate so quickly in humans.
Because viruses are constantly changing, they’re usually difficult to treat, and ultimately, it’s up to the host’s immune system to clear the infection. Vaccinations and antiviral drugs have aided in lowering the mortality rates for these types of diseases, but they’re not always available and can have harmful side effects.
Researchers looking to understand the mechanisms involved here need to find answers that can bring about innovative ways to not only treat these rapidly spreading diseases but also prevent them. Many are finding clues to the viral puzzle by studying epigenetics.
Viral Infections & Epigenetics
Epigenetics is described as the study of both genetic and non-genetic factors that control phenotypic variation. Primarily brought about via external and environmental influence, these modifications alter the activity and performance of a gene without changing the underlying DNA code. In viral-host interactions, DNA/RNA methylation, chromatin remodeling, and histone modifications are known to regulate and remodel host expression patterns.
RNA type viruses, such as COVID-19, show strong associations with RNA modifications. For instance, m6A, m6Am, and 2′-O-me have been found to play important roles in the viral life cycle. In particular, they can affect the structure of the virus, replication, innate immune response, and innate sensing pathways.
Generally, viruses like those from the family of coronaviruses and influenza, are not able to change genetic sequence. However, they can alter the epigenome, allowing them to defeat a host’s immune response and successfully spread infection. Exactly how this occurs is not fully understood. But recent advancements in high throughput technology have allowed researchers to evaluate the epigenetic landscape at a genome-wide scale, as well as on a sequence-specific level. Newer studies are using these technologies and finding that diverse viral groups utilize common and unique strategies to antagonize the immune system.
Coronavirus’s Epigenetic Influence
Coronaviruses include a large family of viruses, and they are common in humans and animals. Most human coronaviruses cause mild to moderate upper-respiratory infections, as in the common cold. But they have also been linked to more severe illnesses such as bronchitis and pneumonia.
According to the CDC, it’s rare for an animal coronavirus to infect people and then spread from person to person. Yet, this has happened before with SARS-CoV and MERS-CoV, and now again with the COVID-19. As well, the Avian Influenza virus (H5N1) and Swine/Variant Influenza (HIN1) spread in the same way. How these viruses sporadically mutated to cause primary and then secondary infections has yet to be determined.
In a study published in 2018 in the Proceedings of the National Academy of Sciences, scientists looking to identify a common avenue used by MERS-CoV and H5N1 in host response found that epigenetic mechanisms were responsible for “switching off” virus-fighting systems. Specifically, DNA methylation was the primary suspect in suppressing the production of antigen presentation molecules in both diseases. As well, histone methylation was involved in lessening immune response in H5N1.
Another study featured in Pathogens pointed out that SARS-CoV and MERS-CoV can delay or offset pathogen recognition, as well as interferon-stimulated gene (ISG) expression levels by encoding unique proteins that prevent immune signaling response. Based on how other viruses like HIV and herpes modulate chromatin, they suggest that these newer viruses may also act similarly. As described in a previous article, Marazzi et al. demonstrated that the influenza-A virus (H3N2) inhibits the immune response of the host by producing a protein that mimics the tail of the histone. By doing this, the protein (NS1) is able to interact with the transcription complex and block the antiviral gene function.
Future Studies Needed
Right now, we are in the midst of fighting one of the most prolific viral outbreaks of the 21st century. Because this one has been so efficient at spreading, it is a reminder of not only how important it is to be prepared, but also more knowledgeable about emerging epidemic-prone diseases.
Future epigenetic studies should expand upon what we already know about these types of viruses so that more specific aspects of immunity, such as inflammatory response and apoptosis, can be explored.
It is important to note that any information gained from these types of studies should be made publicly available across political and international boundaries. Having this information in a rigorous peer-reviewed manner will increase the utility and leverage of already existing data systems, which may be vital in developing both vaccines and therapeutic treatments. Furthermore, it could also allow newly emerging agents to be more promptly identified, and thus control measures put into place sooner.