95% of humans are infected: This virus that can cause terminal illness has no vaccine yet

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95% of humans are infected: This virus that can cause terminal illness has no vaccine yet

95% of humans are infected: This virus that can cause terminal illness has no vaccine yet.

Some people become infected almost undetected, while others develop life-threatening chronic diseases. Why does EBV trigger such a strikingly different fate in human hosts?

Statistically speaking, Epstein-Barr virus (also known as human herpesvirus 4) is lurking in your body right now. It is present in 95% of the world’s population.

The virus is spread through saliva, so maybe when you first got the virus as a baby, the virus came from your mother, and she got the virus from her mother.

Or maybe you caught the virus at the nursery, or from a friend who shared a bottle of Coke with you, or from the pretty girl you kissed at the New Year’s party.

95% of humans are infected: This virus that can cause terminal illness has no vaccine yet

95% of humans are infected: This virus that can cause terminal illness has no vaccine yet

If the last condition infected your young with the virus, EBV can cause infectious mononucleosis , also known as ” kissing disease ,” in which a massive immune response against the pathogen can trigger weeks-long illnesses. Sore throat, fever, and physical weakness. T

he older you get when you get EBV, the worse the symptoms, and we don’t yet know why, but it’s not uncommon in the viral world. If, like most people, you were an infant or young child when you were infected, the initial symptoms were mild enough to be difficult to detect, if not an asymptomatic infection.

So, the virus kept a low profile and infected almost the entire planet. Sometimes people jokingly call it the “everyone virus.” Once inside the human body, EBV will hide in cells and accompany you throughout your life .

Most of the time, the virus is mild and harmless. However, there are always exceptions. Since its discovery in 1964, Epstein-Barr virus has not only been shown to cause infectious mononucleosis, but has also been linked to head and neck, blood and stomach cancers. More controversially, EBV is also associated with some autoimmune diseases.

Two independent studies to be published in 2022 both clearly show that Epstein-Barr virus is the causative agent of multiple sclerosis, a terminal disease that has no cure so far .

Some people become infected almost undetected, while others develop life-threatening chronic diseases. Why does EBV trigger such a strikingly different fate in human hosts?

The virus that accompanies us throughout our lives

Back in the day EBV was discovered, it muddled our stereotypes about viruses. The first person to suspect the existence of EBV was Denis Burkitt , a British surgeon working in Uganda , who had a “deviant” idea that he often saw abnormal jaws in local young children. Bone tumors are caused by unknown pathogens.

These tumors grow rapidly, doubling in size in 24 to 48 hours, and are filled with white blood cells or cancerous lymphocytes. The disease was later called Burkitt ‘s lymphoma .

Burkitt suspected the pathogen because jaw tumors always spread from one area to adjacent areas and followed a seasonal spread pattern. In other words, this lymphoma looks like an infectious disease .

In 1963, a biopsy of cells from a girl with Burkitt lymphoma was sent all the way to the laboratory of British virologist Anthony Epstein in London. His student Yvonne Barr assisted with sample preparation. Under the electron microscope, they saw a uniquely shaped herpes virus — the virus family that also includes the virus behind genital herpes, cold sores and chickenpox — and filled with tumor cells. Case closed? Not yet.

At the time, the idea that viruses could cause cancer was “quite niche”. Alan Rickinson , a cancer researcher who worked in Epstein’s lab in the 1970s, remarked , “There was a lot of skepticism at the time.” Plus, the virus’ ubiquity made the situation quite confusing.

Critics point out that Epstein-Barr virus antibodies are present in children with Burkitt lymphoma, but there is no doubt that other healthy children in Africa also have antibodies.

So do American children, farmers in faraway Iceland, and people from remote tribes in the Brazilian rainforest. Scientists have examined viruses all over the world, while Burkitt lymphoma occurs mostly in equatorial Africa.

Is it possible that the EB virus is just an innocent “bystander”? Why haven’t viruses caused disease elsewhere in the world?

This virus, which almost everyone carries, does cause disease, but scientists don’t know where to check until Goddess of Fortune gives them directions.

In 1967, a technician working on Epstein-Barr virus and cancer in a Philadelphia laboratory became ill, showing symptoms of infectious mononucleosis.

Before that, she was one of the very few people to test negative for EBV antibodies, so she regularly donated blood to the lab with known negative samples.

When she recovered and returned to work, her antibody test turned positive, a very high positive. This hints at what we know today: Epstein-Barr virus is the most common cause of infectious mononucleosis.

Eventually, scientists found more links between the virus and other cancers: nasopharyngeal cancer , stomach cancer , Hodgkin lymphoma , and other forms of lymphoma have all been linked to Epstein-Barr virus. All told, it is responsible for 1.5% of cancer cases worldwide .

The first two cancers caused by Epstein-Barr virus infection appear in cells of the throat and stomach, while others affect white blood cells or lymphocytes, the latter of which are specifically infected by Epstein-Barr virus, especially B cells.

Remember, every B cell in our body is made to recognize a different imaginary enemy.

If a particular B cell never finds an “enemy” that matches itself, it dies and our body ruthlessly eliminates it as a useless immune cell. If the B cell does find a matching “enemy”, it will divide and transform into a memory B cell that will accompany a human throughout his life and guard the human body against infection.

The genius of EBV is to take advantage of this routine process. It manipulates infected B cells into thinking they’ve been activated, so they then turn into long-lived memory B cells in which the virus hides for decades .

This is a special ability shared by the herpes virus family, such as the chickenpox virus, which hides in nerve cells and, when the time is right, causes the carrier to develop shingles.

The Epstein-Barr virus occasionally emerges from its hiding place and replicates itself in just enough numbers to survive—not so little that it gets wiped out by the immune system before finding another host, nor so much that it harms the current host .

The virus and the immune system are in a stable equilibrium and restrict each other. “The virus has established a long-term relationship with the host, which is quite elegant, ” said Sumita Bhaduri-McIntosh , an EB virologist and infectious disease physician at the University of Florida . .

Once this balance is upset, one possible outcome is cancer . As part of manipulating infected cells, Epstein-Barr virus appears to inhibit the normal process of cell death. If the cells that refuse to die have other abnormal characteristics, that person develops a cancer like Burkitt’s lymphoma. “In most cases, when the virus shows up in this cancer, it shows up in other cancers, and it’s one link in the chain,” says Rigginson, “and obviously it’s not the only growth driver. “This also explains why EBV doesn’t give cancer to everyone it infects, only those who are unfortunate enough to also acquire other mutations and other mis-sets at the same time. In the case of Burkitt’s lymphoma, cancer cells also exhibit strange chromosomal rearrangements that scientists know are linked to malaria infection. This explains the unique geographic pattern Burkitt observed: Epstein-Barr virus is ubiquitous, but Burkitt lymphoma is common in areas where malaria is endemic.

Today, Epstein-Barr virus is known to be the first human virus to be associated not only with immediate disease but also with cancers that may appear years after initial infection.

It challenges the traditional paradigm that viruses trigger immunity and cause disease in the short term . After all, it lingers in our body, interacting with our immune system continuously for the rest of our lives.

Cause terminal illness

Over the years, more and more signs of EBV’s unusual abilities have begun to emerge. The virus or its antibodies appear to be biased in patients with autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis, as well as in patients with chronic fatigue syndrome.

The biological mechanisms of these chronic diseases are more elusive than those of cancer, making them particularly difficult to study. The relationship between Epstein-Barr virus and these diseases is still only suggestive and unclear.

All of these patients may have EBV, but so do all healthy people. “With 95% of the world’s population in the control group, that’s not a good start for an epidemiological study,” says Paul Farrell, an EB virus researcher at Imperial College London, UK .

New research by epidemiologist Alberto Ascherio of Harvard University addresses this dilemma, examining a large number of human serum samples collected by the U.S. Department of Defense over more than 20 years (original used to detect HIV) .

Using blood samples from these 10 million adults, the researchers were able to identify a group of humans who were initially EBV-negative but became infected over a 20-year period and were 32 times more likely to develop multiple sclerosis .

The second study, from Stanford University in the US , adds a possible causal link to the correlation: some people with multiple sclerosis have an antibody that both binds to Epstein-Barr virus proteins and recognizes multiple sclerosis A class of brain proteins that are mistakenly attacked by the immune system in disease.

Scientists have long suspected that such an interaction exists, but it has only been confirmed today. “It’s like a giant volcano of information,” says Reginson of the recent study.

However, as with Epstein-Barr virus-related cancers, only a small percentage of people infected with the virus eventually develop multiple sclerosis , so there must be some other trigger or factors at play. We are just beginning to understand the process.

Is it related to the sequelae of the COVID-19?

COVID-19 has also renewed interest in the long-term consequences of EBV infection. Epstein-Barr virus infection is one of the four main risk factors , and some of the long-term sequelae of Covid-19 may be caused by the reactivation of Epstein-Barr virus as the body is weakened by the battle against the virus, a new study of long-term sequelae of Covid-19 found.

How do we judge the danger of this ubiquitous virus? It rarely causes serious illness, but when it does, it can be fatal.

Currently, there is no way we can prevent EBV infection and avoid all the ways humans share saliva: a mother will kiss her child, a toddler might put anything in her mouth. Scientists have been working on a vaccine for decades, and Epstein himself tried it.

Many longtime researchers hope that the virus’s association with multiple sclerosis will reignite enthusiasm for EBV vaccine development.

More than a decade ago, a pharmaceutical company abandoned a vaccine candidate that successfully prevented infectious mononucleosis, but not Epstein-Barr virus infection at the same time . “From a medical economics point of view, this result is very poor,” says Hank Balfour, a pathologist at the University of Minnesota , because only infectious monocytes can be prevented. There is no clear market demand for a vaccine for hyperplasia. However, preventing multiple sclerosis may add additional motivation.

Currently, two of the latest vaccine candidates from the National Institutes of Health (NIH) and Moderna have entered/will enter clinical trials. A key question is whether they are more effective than older vaccines. “Even if we couldn’t prevent infection, we could still reduce EBV-related disease,” said Jeffrey Cohen, an NIH virologist working on one of the vaccines .

However, how to prevent diseases that appear years later, such as cancer or multiple sclerosis, is extremely difficult in traditional vaccine trials.

The incidence of EBV infection is so low, symptoms take a long time to develop, and the vaccine subjects are only a few hundred or thousands, and it is only a few years, and it is difficult to provide clear evidence.

The most likely scenario, Cohen said, is that if the vaccines are effective against infectious mononucleosis, they could be approved to protect people who have not yet been infected with EBV. Once on the market, thousands of people can be vaccinated, and then tracked for years, we can clearly see whether it is effective against cancer or multiple sclerosis.

All of the latest developments point to a “golden time” for EB virus research , said Rigginson, who worked with Epstein, the discoverer of the EB virus . He, who has retired from the University of Birmingham in the UK , said he could no longer pursue it.

Now, it is the turn of the next generation of scientists to solve the remaining mystery of EBV. A better way for humanity to coexist with it may be in the not too distant future.

Reference:
https://www.theatlantic.com/science/archive/2022/03/epstein-barr-virus-mono-cancer-research/623881/

95% of humans are infected: This virus that can cause terminal illness has no vaccine yet

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