Education- Epstein Bar Virus

ProfG has been banging on about EBV as a cause of MS, but what do we know about EBV. 

For me the answer is not a lot. So I thought I would try and educate myself a bit.

The Epstein–Barr virus (EBV), also called human herpesvirus 4 (HHV-4), is one of eight known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. 

Never thought I’ld be saying “I’ve got Herpes”. Now most of us will have to say this as EBV infects 90-95% of the population. Are the other 5% just lucky? or Do they have a defect? 

Epstein–Barr virus infection is spread via saliva, and has an incubation period of four to seven weeks.The virus replicates first within epithelial cells in the pharynx (which causes pharyngitis, or sore throat), and later primarily within B cells (which are invaded via their CD21  receptor. The host immune response involves cytotoxic (CD8-positive) T cells against infected B lymphocytes, resulting in enlarged, atypical lymphocytes (Downey cells).

EBV is best known as the cause of infectious mononucleosis (glandular fever).  T
here may be the presence of an enlarged spleen, and swollen posterior cervical, axillary, and inguinal lymph nodes

Mono most commonly affects those between the ages of 15 to 24 years in the developed World. In the developing World, people are more often infected in early childhood when the symptoms are less. In those between 16 and 20 it is the cause of about 8% of sore throats.  About 45 out of 100,000 people develop mono each year in the United States. Nearly 95% of people have been infected by the time they are adults. The disease is known as “the kissing disease”

It is often treated with anti-biotics, which is useless for an viral disease. 

I suspect glandular fever is causing a “sickness behaviour” because the lymphocytes are expanding and releasing cytokines and causing more B cells to be produced. Then T cells expand to come to kill the virally infected B cells. 

However EBV is also associated with particular forms of cancer such as: 

  • Hodgkin’s lymphoma, In the United States, 0.2% of people are affected at some point in their life. The most common age of diagnosis is between 20 and 40 years old.common symptom of Hodgkin’s is the painless enlargement of one or more lymph nodes, or lymphadenopathy. The nodes may also feel swollen when examined. The nodes of the neck and shoulders are most frequently involved (80–90% of the time, on average). The lymph nodes of the chest are often affected.There are two major types of Hodgkin lymphoma: classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma )NLPHL).Diagnosis is by finding Hodgkin’s cells such as multinucleated Reed–Sternberg cells (RS cells) in lymph nodes. The Reed-Sterberg Cell has its origins in B cells as does NLPHL. 

So it is a B cell that is hyper-proliferating and cell growth is not checked.

  • Burkitt’s lymphoma, is another B cell cancer and is associated with EBV infection in some developing countries.
So again a B cell hyper-proliferation and cell growth is not checked.

Most people become infected with EBV and gain adaptive immunity. In the United States, about half of all five-year-old children and about 90 percent of adults have evidence of previous infection. Infants become susceptible to EBV as soon as maternal antibody protection disappears. Many children become infected with EBV, and these infections usually cause no symptoms or are indistinguishable from the other mild, brief illnesses of childhood. In the United States and other developed countries, many people are not infected with EBV in their childhood years. When infection with EBV occurs during adolescence, it causes infectious mononucleosis 35 to 50 percent of the time.

EBV infects B cells of the immune system and epithelial cells. Once EBV’s initial lytic infection is brought under control, EBV latency persists in the individual’s B cells for the rest of the individual’s life

BV is a relatively uniquely human virus that I guess has co-evolved with human. It has learnt to evade the human immune response for most of the time and infects most humans. However, is it like the papillomavirus and a warty pain in the bum or does it have any useful function? 

My guess it is in fact a bit of both.

My guess it has co-evolved such that it creates long-lived B memory cell responses and so gives survival advantage to the human race, so we tolerate it rather than kill it. We know that EBV can immortalise B cells as we use this technique to make B cell lines and so maybe it helps B cells to live longer and keep immunity. However as a down side it causes a few cancers where B cells do not stop proliferating, it causes glandular fever, which is a consequence of non-cancerous B cells proliferating and it causes MS and a number of other autoimmune diseases, which seem to be a problem of memory B cell. As autoimmunities occur later than when reproduction historically occurred, it is not much consequence to the human population and from an evolutionary prospective the enhanced protective autoimmunity may help the human race more than the influence of  a bit of autoimmunity.

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  • An interesting feature of Hodgkin's Lymphoma is that the nodules contain very few cancer (Reed-Sterberg Cell) cells, they mainly consist of other cells that are normal immune cells. This shows how the infected (cancerous) B cells can significantly affect the immune system. You also get effects in the body a very long way from the site of the cancer eg intense itching of the skin for example.

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