DNA Disruption

SPIKE PROTEIN | EPIGENETICS How Spike Proteins Affect DNA and Gene Expression

DNA’s self-repairing mechanisms act as the ‘guardians of our genes.’ Spike proteins disrupt them.

By Dr. Yuhong Dong

In a study published in 2021 in the Journal of Leukocyte Biology, researchers analyzed genome-wide DNA methylation profiles of peripheral blood from nine terminally ill COVID-19 patients.

Our DNA is made up of a sequence of many genes. Methyl groups (that is, epigenetic factors) are clusters of hydrocarbons that attach to strands of DNA in a biological process called DNA methylation. The process regulates gene expression, as methyl groups act as signals along the DNA, turning genetic activities on and off. Therefore, DNA methylation can change the expression level of a DNA segment without changing its sequence.

Although virtually all cells in an organism contain the same genetic codes (DNA sequences), they don’t express their genes simultaneously or in the same way, so they have totally different functions. That is, the same DNA creates different types of cells, such as liver cells, kidney cells, and nerve cells, through the direction of epigenetic factors.

Epigenetic factors that bind to DNA can directly “turn on” or “turn off” genes. When the genes are “turned on,” they can be expressed and read by the body. Otherwise, they’re “turned off” and can’t be read by the body.

Metaphorically, methyl groups are attached to the DNA like “sticky notes.” DNA can be thought of as a script, which can be amended by putting on (or taking off) some sticky notes over its text.

The Journal of Leukocyte Biology study results suggest that the SARSCoV-2 virus can dramatically reshape peripheral blood and lung tissue host immune cell landscapes and may modify cellular DNA methylation states. SARS-CoV-2 can possibly alter other epigenetic mechanisms, such as histone modifications and noncoding RNA.

The researchers discovered a distinct DNA methylation signature of severe COVID-19 that showed dramatic cell-type composition changes, hypermethylation of IFN-related genes, and hypomethylation of inflammatory genes.

Interferons (IFN) are so named because they “interfere” with viruses and prevent them from multiplying. They’re proteins that inform our immune system that germs or abnormal cells (such as cancer cells) are present in our body and trigger killer immune cells to destroy them.

Blanco-Melo et al. examined the transcriptional response to SARSCoV-2 within in vitro infected cells, infected ferrets, and post-mortem lung samples from lethal COVID-19 patients and reported that IFN-I and -III responses are attenuated.

In addition to the level of expression of IFN-I, the timing of the IFN-I response is also a critical factor in determining the outcomes of infection. An early and potent cellular IFN response is vital for the antiviral response, whereas a delayed IFN-I response contributes to pathological inflammation and severe outcomes.

Accordingly, a timely early switch “on” of IFN-related genes is a critical factor for the human body to overcome the virus invasion and minimize the severe outcomes of the disease.

Epigenetic Mechanism of Gene Regulation

Chromosomes

Histone modification

Epigenetic factors

Spike Proteins Enter Cell Nuclei, Impair DNA Self-Repair

A research paper published in October 2021 in the journal Viruses states that the SARS-CoV-2 virus’s spike proteins can impair the body’s DNA damage-repair mechanism. The researchers also were surprised to find an abundance of spike proteins in the cell nuclei.

It’s well-known that only certain

DNA methylation regulates gene expression, as methyl groups act as signals along the DNA, turning genetic activities on and off.

DNA

Histone

Genes (o )

150%

DNA methylation

DNA 100% Genes non-homo logous end (o ) joining (NHEJ) 50% e ciency

Methyl groups

0% Emptyvector Spike protein (full-length) Spike protein S1 Spike protein S2

SOURCE: NATIONAL INSTITUTES OF HEALTH

types of proteins can possibly be transported into a human cell nucleus, such as histones, DNA and RNA polymerases, and gene regulatory proteins. The nuclear envelope encloses the DNA by double membranes, and there are complex gatekeepers present in the nuclear membranes to prevent the entry of unwanted substances into the cell

DNA methylation regulates gene expression, as methyl groups act as signals along the DNA,

Spike Proteins Damage Cells, lmpairing DNA Damage Repair

150%

DNA non-homo logous end joining (NHEJ) e ciency 100%

50%

0% Emptyvector Spike protein (full-length) Spike protein S1 Spike protein S2 150%

DNA homologous recombination (HR) e ciency 100%

50%

Emptyvector Spike protein (full-length) Spike protein S1 Spike protein S20%

SOURCE: VIRUSES

nucleus, where most DNA repair occurs.

When DNA is replicating itself, potential errors can be made. However, fortunately, we have innate DNA self-repairing mechanisms, which act as “guardians of our genes.”

To their surprise once again, the study’s researchers discovered that spike proteins significantly suppressed the DNA self-repairing mechanisms, including homologous recombination (HR) and non-homologous end joining (NHEJ).

The researchers also found that the spike proteins stayed in the cell nuclei and significantly inhibited DNA damage repair by impeding key DNA repair proteins from gathering at the damage site and by interfering with double-stranded DNA break (DSB, a principle cytotoxic lesion) repair.

The findings from the aforementioned studies indicate that the spike protein is an unusual protein that can impact the epigenetic function of our human cells.

EXAMPLES OF EPIGENETICS AND DISEASE

150%AGING: The aging process is regulated by epigenetic factors. Due to scientific advancements, DNA 100% biomarkers of aging based on homologous DNA methylation data can be 50% recombination (HR) e ciency used to accurately estimate the age of tissues. A genome-wide DNA Emptyvector Spike protein (full-length) Spike protein S1 Spike protein S20% methylation study published in April in the journal Nature Communications collected whole blood samples from 232 healthy individuals, 194 nonsevere COVID-19 patients, and 213 severe COVID-19 patients. Researchers discovered that the epigenetic age of COVID-19 patients was significantly accelerated.

NEURODEGENERATIVE

DISEASES:

Extensive research has suggested that DNA methylation plays an important role in the cause and development of Alzheimer’s disease. A team of researchers from the University of Oxford and the University of Cambridge performed an analysis of two-year retrospective cohort studies by examining the medical records of 89 million patients, including both COVID-19 patients and patients with other respiratory diseases at a ratio of 1:1. It was discovered that throughout the two-year follow-up period, COVID-19 patients were persistently at an increased risk of psychiatric disorder, cognitive deficit, dementia, and epilepsy or seizures.

AUTOIMMUNITY: The link between epigenetics and autoimmunity has already been well-documented in scientific literature. Epigenetic changes, such as DNA methylation and noncoding RNAs, have been discovered to play a role in the pathogenesis of autoimmune diseases, mainly by regulating gene expression.