Clinical Researchers’ Discovery May Lead to Epstein-Barr Virus Vaccine
There are elements in the way our body’s immune system and infecting viruses (or bacteria) play ‘hide and seek.’
One instance of this – the infection by the Epstein-Barr virus – led researchers at the Child and Family Research Institute (Vancouver, British Columbia, Canada) to discover a potential way of ‘unhiding’ the Epstein-Barr virus (EBV) so that the immune system can attack it.
For the most part EBV causes relatively minor discomfort, if any, similar to a normal flu or cold episode. It is rarely diagnosed, except in the cases where it causes infectious mononucleosis.
This form of mono appears almost exclusively among teens and young adults, where it causes fatigue, headache, fever, sore throat and swollen lymph glands. It generally runs its course without much more than treating symptoms, although occasionally leads to serious complications.
Of greater concern is the ability of EBV to trigger certain types of cancer, mainly Burkitt’s lymphoma (cancer of the lymph glands) and nasopharyngeal carcinoma (cancer at the top of the throat at the passages to the nose). These types of cancer are generally rare (less than 1 case per 100,000 in most countries) but are the most common form of cancer in China (18% of all cancers).
While ‘hiding’ from the immune system is common among pathogens, EBV is a prominent example because once a person becomes infected (at any age, often as children), it stays in the bloodstream until death. It is estimated that in the United States, of people between 35 and 40 years old, 95% are infected.
In fact, the EBV virus hides out in the cells of the immune system itself. It infects the so-called B cells (beta leucocyte) or white cells. It is more than a little ironic these are the cells the immune system uses to, among other things, store a biological memory of previous infections. The question for scientists was how does EBV infect these cells and remain undetected for so long?
The answer, provided by the British Columbia research, is that EBV turns off the production of specific proteins in the B cells, proteins that would normally provide markers for viral infection. Technically, these markers are part of the immune system that encodes activation for infectious diseases as ‘memorized’ in the B cells. Without these proteins, the virus can sit in the B cell and not activate detection by T cells, the immune cells that do the job of killing infected cells.
The researchers were able to isolate this effect by using infected cells from the tonsils removed from patients. They added T cells (NKT cells) to the EBV infected B cells and found that the more T cells added, the fewer EBV infected cells, which demonstrated the presence of EBV in the B cells. Further experimentation led to identifying the proteins ‘silenced’ (i.e. their production is shut off by inhibiting the gene for their production) by EBV.
The next step in the research is to find one or more ways to re-activate these silenced proteins, so that infected cells no longer ‘hide’ and can be attacked by T cells. Another alternative would be to use the silenced proteins as markers for infection and introduce a different or manmade antigen to attack those cells.
The researchers also hope that the discovery of how EBV hides within the immune system may also unlock other forms of bacterial or viral ‘camouflage, ‘ that is, reveal a more general mechanism.
Although it is still many years down the research road, the hope is that a vaccine to treat EBV and similar infections will use the knowledge of the immunization silencing proteins.