When Life Asserts Its Power on the Smallest Scale

When Life Asserts Its Power on the Smallest Scale

With a microscopic view of our surroundings, we step into a realm of the unknown—a world where countless microorganisms thrive, each telling a different story of life’s complexity. Among them, viruses, despite their relatively simple structure, remain some of the most enigmatic entities in existence. These beings blur the line between life and non-life. Their survival depends entirely on their unfortunate hosts, and outside their target cells, they are nothing more than dormant genetic packets.

Viruses do not breathe, eat, or even reproduce on their own. Yet, these seemingly harmless entities come to life the moment they find their target cell. By taking full control, they transform it into a factory dedicated to producing more copies of themselves. These cellular factories can be bacterial, plant-based, or from any living organism. But our story begins when human cells fall prey to an opportunistic virus.

Infiltrating the Heart of Immunity

If you were told about a virus that has infected over 90% of people worldwide, what would be your first guess? You might think of viruses like COVID-19 or the varicella-zoster virus (which causes chickenpox). But this time, the discussion is about a different virus—Epstein-Barr virus (EBV). This virus circulates widely among humans, and many of us have encountered it without even realizing it.

EBV stealthily enters our bodies through the mouth. Its first stop is the epithelial cells of the throat, where it begins replicating—especially in individuals with a weakened immune system. After this initial phase, the virus moves toward its primary target: B lymphocytes, which are crucial cells of the immune system. However, instead of defending the body, these infected B cells become safe havens for EBV. At this point, the lytic phase begins—a stage in the virus’s life cycle characterized by high activity and rapid replication. During this phase, EBV aggressively invades host cells, hijacking them to produce more viral copies.

Ultimately, this virus can cause a range of illnesses, from mild infections to severe diseases. Some of the conditions associated with EBV include respiratory infections, infectious mononucleosis, Kawasaki disease, and even certain types of cancer. More broadly, EBV has been linked to oncogenesis (cancer development) and autoimmune diseases, as it can induce genetic changes in cells, leading to uncontrolled proliferation.

One of the biggest challenges with EBV is the complexity of diagnosis and treatment. Since many of its early symptoms resemble those of other viral infections, timely and accurate diagnosis can be difficult. A diagnostic delay increases the risk of long-term complications or progression to more severe conditions.

The Body Takes Action

To replicate, Epstein-Barr viruses (EBV) require specific proteins, such as BZLF1 and BRLF1. The production and release of these proteins act as an alarm signal for the immune system, alerting key immune cells- particularly cytotoxic T cells (killer T cells)- to the infection. These veteran soldiers of the immune system recognize and destroy virus-infected cells, preventing further viral spread. This immune battle manifests in some individuals as symptoms like fever, sore throat, and fatigue, creating the classic picture of infectious mononucleosis.

Over time, as the immune system gains partial control, most of the virus is eliminated. However, EBV does not surrender easily. Instead, the remaining viruses enter a latent phase, stealthily hiding within B lymphocytes, where they lay low and strategize their next move.

From a Simple Infection to a Complex Disease

EBV is a silent and mysterious guest, often lingering in the body for years without causing noticeable symptoms. However, recent research has uncovered a disturbing possibility—this virus may contribute to the development of severe diseases, including multiple sclerosis (MS).

MS is an autoimmune disease, meaning that the immune system mistakenly identifies the body's own cells as enemies and attacks them. In this case, the central nervous system (CNS) becomes the battleground, and the mistaken targets are oligodendrocytes—cells responsible for supporting and insulating nerve fibers. The resulting inflammation and damage disrupt neural communication, leading to serious neurological impairments.

The exact cause of MS remains unknown, but researchers believe it results from a combination of genetic and environmental factors. Among the potential environmental triggers, EBV has been a major focus of scientific investigation.

Samia Khoury, a leading MS researcher, has extensively studied the role of EBV in MS pathogenesis. She states: "There is a significant association between Epstein-Barr virus positivity and the risk of developing MS."

A Look at Samia Khoury’s Research

Khoury’s scientific research seeks to unravel complex mysteries by focusing on the study of exosomes in the serum of MS patients. Exosomes are tiny particles (about 30 nanometers in diameter) that act as microscopic messengers, transferring biological molecules -such as proteins and lipids- from one cell to another.

Regarding the exosomes found in MS patients, Khoury states: "We discovered that the serum exosomes of MS patients, especially during active disease phases, express Epstein-Barr virus (EBV) proteins. Moreover, exosomes carrying these proteins were able to activate monocyte-derived macrophages outside the cells."

In other words, the presence of EBV proteins such as EBNA1 and LMP1 in the exosomes of MS patients indicates that the virus is active within their bodies. Furthermore, the findings revealed that these EBV-positive exosomes trigger the release of cytokines -immune signaling molecules- from macrophages, a type of immune cell. This amplifies inflammation, ultimately contributing to the development and progression of MS.

Exploring Other Possible Mechanisms Linking EBV to MS

One of the proposed mechanisms by which Epstein-Barr virus (EBV) may contribute to multiple sclerosis (MS) is molecular mimicry. In this process, due to the similarity between EBV proteins and the body’s own proteins, the immune system becomes confused. When it produces antibodies against the virus, these antibodies may mistakenly attack the body's own proteins.

For instance, BFRF3, a protein found in the EBV viral envelope, closely resembles Septin-9, a crucial human protein involved in cell structure and function. As a result, when the immune system encounters EBV, it generates antibodies against BFRF3. However, due to their similarity, these antibodies may also target Septin-9, leading to the destruction of supportive cells in the nervous system and increasing the risk of MS.

Another proposed mechanism is abnormal B cell activation. EBV can manipulate B lymphocytes using proteins like LMP1 and LMP2A. These viral proteins mimic normal immune signals, tricking B cells into excessive growth and replication. The consequence is the production of a large number of abnormal or dysfunctional B cells, which may contribute to autoimmune diseases like MS.

Additionally, EBV can cause indirect damage. When immune cells become highly activated to combat the virus, they may unintentionally harm nerve cells. This situation is comparable to a battle where friendly fire damages the body's own structures, further fueling the inflammatory process associated with MS.

The Mystery of Immunity

If nearly everyone is infected with EBV, why do only a small percentage develop multiple sclerosis (MS)? As previously mentioned, MS is influenced by a wide range of genetic and environmental factors, meaning EBV alone cannot fully explain its development.

For example, some individuals carry defective versions of certain genes, such as those involved in producing HLA (human leukocyte antigen) proteins. HLA proteins display cellular proteins on the cell surface, acting as an immune surveillance system. If a cell contains abnormal proteins -due to infection or mutations- HLA presents them as a warning signal to the immune system. However, mutations in HLA genes can cause the immune system to mistakenly recognize the body’s own proteins as threats, triggering autoimmune reactions.

Beyond genetics, environmental factors like vitamin D levels, smoking, and geographical location also play significant roles. EBV infection is only one piece of this complex puzzle—for MS to develop, a unique combination of genetic predisposition and environmental triggers must align. These intricate interactions explain why some individuals with EBV remain completely healthy, while others develop one of the most serious autoimmune diseases.

While the link between EBV and MS still requires further research, each new discovery brings us closer to understanding and combating the disease. Samia Khoury's research not only sheds light on this complex relationship but also paves the way for more targeted treatments and potential vaccines. Perhaps one day, not just MS but many other diseases will be fully controlled, freeing future generations from the shadow of these health threats.

This article was previously published in the second issue of the Observatory magazine.