Most of us have heard of the the “kissing disease”—that highly contagious condition known as mononucleosis or “Mono”. But did you know that it’s caused by Epstein Barr Virus (EBV)?
While we’ve heard about the sore throat, the heavy fatigue, the lost school days, the swollen tonsils, and the body tenderness that can last for days and weeks, the conversation about mononucleosis tends to stop there.
But for many people EBV can get reactivated later in their life, without them ever knowing.
EBV is a gamma-herpes virus also known as human herpesvirus 4. EBV is estimated to infect as much as 98 percent of the world’s population. While the history of EBV spans over five decades, only within the last five to ten years have we started to understand some of the possible mechanisms of how EBV may lead to long-term health complications.
While EBV is most widely known as the causative agent of infectious mononucleosis, researchers have identified a number of mechanisms of how the EBV infection may increase risk of autoimmunity as well as some cancers. While general infections may trigger autoimmune disease, there may be a long lag between initial infection and the onset of disease.
Through new understandings of epigenetics and the reality of coinfections—researchers are just beginning to piece together why EBV remains latent in some people, but reactivated in others. Researchers are also curios as to why some people get autoimmune diseases and/or cancer, while others have few, if any, long-term complications.
EBV and Autoimmunity
EBV is implicated in a number of autoimmune disorders including Systemic Lupus Erythematosus (SLE), multiple sclerosis, autoimmune thyroiditis, rheumatoid arthritis (RA), inflammatory bowel diseases, insulin-dependent diabetes mellitus, Sjogren’s syndrome, myasthenia gravis, as well as autoimmune liver diseases such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis.
While exposure to some infections while we are young may actually protect us against autoimmunity, EBV appears to largely trigger immune problems when compared to the long-term effects of similar herpes viruses and infections.
Authors are careful to note that infectious agents may work both alone as well as in additive and synergistic concert with other immune, genetic, dietary, and environmental factors.
Three mechanisms that are thought to link EBV as a trigger of autoimmunity are:
1. Molecular Mimicry
Molecular mimicry is when the immune system mistakes self-proteins as a foreign pathogen. Protein sequences found on pathogens and their byproducts, may mirror similar sequences on healthy tissue. EBV may induce systemic lupus erythematosus via molecular mimicry. EBV antigens are known to cross-react with lupus-specific antigens. EBV infection has been implicated as an autoimmune trigger involved in the development of Parkinson’s disease through molecular mimicry with the neural protein alpha-synuclein.
2. Bystander Activation and Cryptic Antigens
Bystander activation is a process by which immune cells are activated indirectly due to the inflammatory environment induced by an infection—like a domino effect.
Additionally, the inflammation can lead to the breakdown of proteins exposing what researchers call cryptic antigens. Cryptic antigens are protein sequences that are normally hidden from our immune system yet become visible and acted upon in the midst of pathogen-induced inflammation.
3. EBV Immune Evasion and Persistence:
Additionally, EBV may allow reactive immune cells to persist longer in the body. This is due in part to EBV’s invasion of immune cells known as B cells which continue to replicate, and become memory B cells that can persist for life. These infected memory B cells build up in tissues—and may lead to rises in autoreactive T-cells. The T-cells can also release inflammatory cell messengers such as lymphotoxin, tumor necrosis factor-alpha, interleukin-1Beta, and IL-6—ultimately contributing to autoimmune damage in susceptible tissues.
EBV can evade the immune system by producing proteins that inhibit a number of the body’s immune defenses and prevent programmed cell death. When cell growth is overstimulated, and healthy cell-death is blocked, cell overgrowth occurs. Cell overgrowth is generally known to us as cancer.
EBV-infected cells also may release particles that are also sensed by dendritic cells during primary infection. The dendritic cells then coordinate short-term and long-term immune responses to the virus .
Due to the complexity of EBV’s life cycle, researchers have yet to develop an effective vaccine, but new insights on the role of dendritic cells may offer them more clues.
EBV and Cancer
Due to the EBV’s ability to persist long-term in immune cells, EBV may increase the risk for lymphoma and other lymphoproliferative diseases where the body loses control of the growth of certain immune cells. Lymphoproliferative diseases have also been associated with cases of SLE, RA, and Sjogren’s Syndrome—potentially demonstrating another link between EBV and immune disorders.
EBV was the first virus to be identified as a carcinogen. It is known to play a role in Burkitt’s lymphoma, Hodgkin’s disease, non-Hodgkin’s lymphoma, nasopharyngeal carcinoma, lymphoma, and leiomyosarcomas in susceptible individuals.
EBV may also play a contributing indirect and direct role in breast cancer development. One investigation used laboratory analysis to determine that EBV genetic material was present in at least 20 percent of breast tumors studied.
Similarly, other work has demonstrated evidence of possible EBV involvement in gastric carcinoma due to its presence in immature cells that line the stomach. Due to EBV’s influence, the immature cells are not “allowed” to mature into their target cell types—therefore they persist and develop the potential for cancer to develop. As much as 10 percent of gastric cancers are also now believed to be caused by viruses such as EBV.
The Epigenetic Role Of Coinfections
Infections such as EBV do not occur just by themselves. You can have multiple infections going on at once. If you are stressed and your immune system is compromised, not only can this lead to an active infection of EBV, but other infections as well.
Other reported coinfections include respiratory syncytial virus, Chlamydia pneumoniae, human herpesvirus 6, measles virus, parainfluenza virus, influenza, Mycoplasma pneumoniae, adenovirus, Haemophilus influenzae, Klebsiella pneumoniae, parvovirus B19, and Legionella pneumophila. EBV may also complicate cases of HIV and AIDS.
We used to think that we were fated by our genetics. Epigenetics is the new science of how environmental signals alter how our genes are expressed. Based on our conventional understanding of genes, we know that you can have lower or higher probability of developing certain diseases. Epigenetics is the study of how those probabilities are triggered by influences from our environment, psychology, and diet.
While you may have EBV in your system, for most people it is inactive and dormant. In the presence of coinfections, however, EBV may be reactivated through epigenetics. In this case it is the presence of other infections that acts as the epigenetic trigger.
For instance, a bacterial infection may lead to a natural increase in lymphocytes to the infected area. EBV and its byproducts are found inside lymphocytes, increasing the chances for interactions between EBV-infected lymphocytes and byproducts of the coinfection.
Byproducts from each infection potentially feed activation of the other. The interactions may also favor a more robust immune response. An overactive immune response increases the risk of friendly fire against your own cells.
Similar epigenetic interactions may help link the association of EBV with periodontitis—which appears to play a role with the coinfection Porphyromonas gingivalis. EBV may also interact with Helicobacter pylori infection—modulating the risk of gastric cancer.
Genes often code for certain functions in the body. In one person, a biochemical pathway may be faster or slower based on their epigenetics. One important pathway in the body is methylation.
Methylation is the body’s way of activating, removing, or recycling certain compounds in the body. Altered methylation is one epigenetic example of why someone may be at higher risk for EBV infection in the first place, but then long-term, may also influence why EBV remains latent for some, and reactivated in others.
EBV Reactivation and Protective Remedies
The mechanisms of EBV reactivation remain largely unclear. Physical or mental stress, as well as the immunosuppression associated with aging may trigger EBV reactivation. As discussed earlier, coinfections may also alter the long-term course of EBV.
While a wide range of immune strategies may be helpful in reducing the potential burden of EBV reactivation, a few natural therapies may offer specific support.
Vitamin D may work directly against enveloped viruses which include EBV, CMV and other coinfections and may offer a role as a therapeutic and preventative agent. Vitamin D levels may correlate inversely with EBV activity and modulate risk for other immune complications such as multiple sclerosis.
Intravenous vitamin C therapy may also have a positive effect on EBV infection. As patients with higher levels of vitamin C have lower EBV antigen levels.
Monolaurin, a lipid extract from coconut oil, has shown anti-viral activity against enveloped viruses including EBV, CMV, and other herpesviruses. Monolaurin may work by disintegrating the protective lipid envelope surrounding EBV and other herpes viruses.
If epigenetics is leading us in the right direction, tackling an active or reactivated EBV infection may become less of a conversation about finding specific remedies to boost the immune system, and much more of a conversation about optimizing your personal biochemistry, identifying co-infections, and promoting stress balance.
Submit your story or essay to Buzzworthy Blogs.