EB Virus Could Be Infected by Kiss: A Hidden Threat Linked to Cancer

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EB Virus Could Be Infected by Kiss: A Hidden Threat Linked to Cancer

EB Virus Could Be Infected by Kiss: A Hidden Threat Linked to Cancer

It has been revealed that 95% of the world’s population is infected with the mysterious pathogen “EB virus,” which easily spreads through kissing and is known to cause various types of cancer.

There is a virus known as the “kissing disease,” which is the Epstein-Barr virus (EBV), often spread through kissing.

The Epstein-Barr virus (EBV) is a type of DNA virus discovered by two scientists, Epstein and Barr, hence the name. It belongs to the Herpesviridae family of double-stranded DNA viruses and is also known as Human herpesvirus 4 (HHV-4). It is transmitted through saliva, and most people become infected with this virus by adulthood. While many people are asymptomatic when infected, the virus remains in the body and becomes latent.

EB Virus Could Be Infected by Kiss: A Hidden Threat Linked to Cancer

In some individuals, primary infection can cause infectious mononucleosis, where the virus infects lymphocytes, causing swelling of the liver, spleen, and lymph nodes, along with symptoms similar to a cold, such as fever and sore throat. This disease resolves on its own, but the virus continues to persist in the body in a latent form. While the main infected cells are lymphocytes, the virus can also infect epithelial cells.

The virus is mainly present in bodily fluids, particularly saliva. The infectious mononucleosis caused by EB virus often spreads through kissing, hence its nickname “kissing disease.” It is often observed in young people, especially after entering university or joining the military, where close contact is common.

In this disease, the virus infects B lymphocytes, leading to a temporary rapid increase in lymphocytes, causing swelling of lymphoid tissues, especially lymph nodes and the spleen. Therefore, diagnosis requires palpation to check for swelling of lymph nodes and the spleen. However, the spleen that swells during infectious mononucleosis is soft, so it can easily rupture under external pressure.

One of the authors remembers a lesson from his medical school days during internal medicine clinical training, where he was told to be careful when suspecting EB virus infection in young patients. This caution was due to the risk of the spleen rupturing if inexperienced residents applied too much pressure during palpation (if the spleen ruptures and is left untreated, it can lead to hemorrhagic shock). This was a memorable lesson in the importance of moderation.

EB virus as a cause of various cancers

The EB virus can cause various diseases, including cancers, in some infected individuals. For example, it can cause nasopharyngeal carcinoma and malignant lymphoma.

Nasopharyngeal carcinoma caused by the EB virus is a cancer that occurs in the epithelial cells lining the nasopharynx, the airway for breathing through the nose. It is more common in Asia, particularly in southern China, Taiwan, and parts of Southeast Asia.

On the other hand, malignant lymphoma caused by the EB virus is often derived from NK cells, a type of lymphocyte, and is frequently seen in East Asia, including Japan.

It is not well understood why the same EB virus can produce different types of tumors. Recent genomic analysis of latent EB virus infection suggests that the strains of EB virus in southern China, Southeast Asia, and those in East Asia, including Japan, belong to different groups. It is possible that different diseases may occur depending on the types of EB virus strains distributed in these regions.

In general, viruses cause diseases in humans by destroying infected cells when they produce their offspring particles. However, carcinogenesis by the EB virus is somewhat different. While in a latent infection, the EB virus can immortalize and transform infected cells into cancer cells by expressing a limited set of viral RNAs and proteins.

The abnormal cell proliferation and cancer pathology caused by the EB virus are extremely diverse and difficult to grasp. Each pathological condition has different patterns of viral gene expression, and the mechanisms of abnormal proliferation and carcinogenesis are also different.

The common feature is that the infected cells in latent infection are actively dividing cells, unlike neurons infected by varicella-zoster virus, which hardly divide. Therefore, during cell division, the viral DNA genome also replicates and is inherited by the daughter cells.

Furthermore, during this latent infection, the virus does not always produce viral particles (i.e., does not destroy cells) but instead expresses various viral RNAs and proteins, gradually altering the intracellular and extracellular environments, and accumulating mutations in the human chromosomes of the latent infected cells. This accumulation ultimately leads to the transformation of cells into cancer cells.

Recently, it has been reported that latent EB virus infection may be one of the causes of multiple sclerosis, a neurological disease. Multiple sclerosis is a rare disease characterized by inflammation in the central nervous system and is often referred to as MS, derived from its English name, multiple sclerosis. Due to inflammation, the myelin sheath covering the nerves breaks down, leading to demyelination (exposing the inner wire) in various parts of the central nervous system. After the inflammation subsides, scars harden in various parts, hence the name multiple sclerosis.

Multiple sclerosis presents with neurological symptoms such as motor dysfunction, sensory impairment, and dementia. It is estimated that there are about 20,000 patients in Japan, and it is a rare disease for which no effective treatment has been found so far.

One study demonstrating the relationship between EB virus and multiple sclerosis followed more than 10 million young soldiers in the American military for over 20 years, closely examining about 1,000 individuals who developed multiple sclerosis. According to the study, all but one of the multiple sclerosis patients were EB antibody positive.

Furthermore, among the 35 cases with stored sera, a staggering 34 cases had developed multiple sclerosis after EB infection. Additionally, the serum marker neurofilament light chain, indicating damage to nerve axons, began to rise after EB infection, and individuals infected with EB had a 32-fold higher risk of developing multiple sclerosis compared to other virus-infected individuals. In other words, EB infection may trigger neurodegeneration, leading to the development of multiple sclerosis.

So why does EB virus infection lead to neurodegeneration? A recent study from the United States has reported intriguing results. According to the study, some B lymphocytes (cells that produce antibodies) derived from multiple sclerosis patients produce antibodies against one of the EB virus’s transcription factors, EBNA1.

These antibodies also bind to a specific protein called GlialCAM, which is expressed in glial cells that surround nerve cells. This means that antibodies against the EB virus also reacted with a self-antigen (moreover, an antigen specific to the nervous system) called GlialCAM.

This phenomenon is called molecular mimicry, where an antigen from a virus, EBNA1, and a self-antigen, GlialCAM, structurally resemble each other, leading to an immune response against the viral antigen also affecting glial cells. In simple terms, the immune response against the viral antigen mistakenly attacks one’s own nerve cells because the viral antigen and the self-antigen are virtually identical.

It is possible that in some individuals, EB virus infection results in the production of anti-EBNA1 antibodies, which bind to glial cells, leading to attacks on the nervous system and the development of multiple sclerosis.

Certainly, if such events occur after EB virus infection, inflammation in the nervous system may continue. However, normally, the blood-brain barrier prevents antibodies produced by the immune system from entering the brain. Additionally, it is unclear why inflammation in the nervous system occurs only in some individuals.

Herpesviruses that cause latent infections generally tend to cause more complications when first infected during adolescence or adulthood compared to infection during infancy. The paper on the development of multiple sclerosis following EB virus infection is a good example.

While approximately 95% of the world’s population is infected with the EB virus, the development of multiple sclerosis is almost rare. However, of the 35 individuals whose infection progress was tracked, 34 individuals were found to have been infected with the EB virus after reaching adulthood (after joining the US military) and subsequently developed multiple sclerosis. Primary EB virus infection in children is often asymptomatic, but primary infection during adolescence makes individuals more susceptible to developing infectious mononucleosis.

Furthermore, individuals who develop infectious mononucleosis are more likely to develop Hodgkin’s lymphoma or multiple sclerosis compared to those who do not develop infectious mononucleosis. In a large-scale follow-up study from Germany, it was also found that among EB virus-infected individuals, those who developed infectious mononucleosis were more likely to develop blood or lymphatic system tumors in the future.