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Coronavirus

Epigenetics and coronaviruses

The interactions of coronaviruses and epigenetic processes of a human cell have been an area of study for years, especially after similar outbreaks from SARS and MERS. A review paper in Pathogens Epigenetic Landscape during Coronavirus Infectionillustrates how coronaviruses may alter a host cell’s transcriptional apparatus and thus regulate DNA replication and transcription. Epigenetic changes such as histone modifications, DNA methylation, chromatin remodeling, and non-coding RNAs function as important regulators that alter host expression patterns. These changes have important implications to the virus itself since it relies on the host cell to replicate its genetic material and continue to proliferate.  As researchers begin to understand how epigenetics may prevent viral proliferation, vaccines and therapeutics can be developed to specifically target a virus’ replicating mechanisms.  

Areas of significance for epigenetics and coronaviruses


Testing

Mount Sinai’s Icahn School of Medicine and other medical institutions have been developing an epigenetics test  for early detection of the coronavirus that causes COVID-19.The test identifies disease-specific DNA methylation signatures from blood samples to distinguish between pathogenic mutations and benign variants.  

Immune system response

The molecular mechanisms that regulate virus to host interactions are associated with entry, replication, and innate immune response. Recent evidence implies that viruses have developed processes that regulate the host epigenome and control host immune antiviral defense processes, thereby promoting pathogenesis.  

Understanding severity of disease

Epigenetics may play a key role in the severity of symptoms in COVID-19. During the first line of defense, the immune system releases cytokines during infection, and excessive amounts of the protein (the cytokine storm) have been linked to severe COVID-19 symptoms. In a recent study from Clinical Immunology researchers studied the epigenetic regulation of cytokines in people with lupus and found that key cytokine genes were hypomethylated, resulting in excessive cytokine production. The different epigenetic regulation of cytokines may explain disease severity in lupus patients.  

Understanding susceptibility

Researchers have determined that a number of conditions including diabetes, hypertension, cardiovascular disease, obesity and lung disease present risk factors for COVID-19 infection.  According to Dr. Andrew Feinberg at Johns Hopkins Medical in “Epigenetics and the Adaptive Genome in a Changing Environment,” various risk factors for specific diseases can be quantified by analyzing DNA methylation of specific genes and other epigenetic markers.

To illustrate, clinicians have found that a compromised immune system, as observed in lupus patients, might be especially prone to severe COVID-19.  Recent insights suggest that the hypomethylation and overexpression of ACE2, which encodes a functional receptor for the SARS-CoV-2 spike glycoprotein, results in enhanced viral infection. In addition, demethylation NFκB and key cytokine genes in these patients increases chances of cytokine storm. This suggests that epigenetic dysregulation in lupus might facilitate viral entry and an excessive immune response. Epigenetic control of ACE2 might be a viable method for prevention and therapy in COVID-19..  

How Diagenode can help

Deeper study into the epigenetics of the COVID-19 infection could help clinicians to detect the virus more accurately, assess risk and severity of disease, as well as personalize treatment options across varying patient profiles. New research of epigenetic adaptations could better uncover predictive markers, new targets and the associated mechanisms of SARS-CoV-2 and COVID-19.

Diagenode offers tools to help in a number of areas for SARS-CoV-2 research:

DNA methylation profiling, bioinformatics, and data mining

  • Uncover host DNA methylation changes caused by the virus RNA
  • Large human cohorts studies, biomarker discovery for survival / susceptibility

Long read sequencing

  • Characterize genomic regions that are important in immune response in humans to elucidate the variance observed in the severity of response to SARS-CoV-2 infections. 
  • Characterize the viral genome 
  • Understand viral mutations

Mechanistic studies

Mechanistic studies where histones/chromatin play a role: Histone modification antibodies and ChIP kits or Chromatin Profiling Services

References

Corley, M. J., & Ndhlovu, L. C. (2020). DNA methylation analysis of the COVID-19 host cell receptor, angiotensin I converting enzyme 2 gene (ACE2) in the respiratory system reveal age and gender differences. Preprints.

Sawalha, A. H., Zhao, M., Coit, P., & Lu, Q. (2020). Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients. Clinical Immunology.

Schäfer, Alexandra and Baric, R. (2017) Epigenetic Landscape during Coronavirus Infection. Pathogens https://doi.org/10.3390/pathogens6010008

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