Most of us have already had an encounter with the Epstein-Barr virus, or EBV, for short. As part of the herpes family, it's one of the most common disease-causing viruses in humans. We get the disease with (or without) some nasty symptoms, then we recover. However, EBV stays in our body after the illness has ended, and it's one of the few viruses known to cause cancer.
About 90% of us still have EBV in our bodies from a past infection — like, say, getting infectious mononucleosis (mono) as a teen — and it will never bother us again. Researchers have been struggling to figure out what mechanisms EBV uses to stay in our cells when our immune system should have removed it, as well as if EBV uses that process to cause cancer.
New research by a team from Duke University's School of Medicine describes how EBV manages to persist in the body despite our best attempt to get rid of it. Their work appears in the open access journal eLife.
The Many Faces of EBV
After the swollen nodes, fever, and extreme fatigue of mono subside, most of us forget about EBV and will never have to deal with it again. That is unless something like chemotherapy drugs or an organ transplant suppresses our immune system.
Children who receive an organ transplant get a 200 times higher risk of developing non-Hodgkins lymphoma, cancer of the lymphatic system, that can be caused by EBV.
The research team, led by study researcher Micah A. Luftig, the deputy director of Duke's Center for Virology, found that a type of white blood cell called B lymphocytes are both infected and quickly manipulated by the virus for its advantage. The process they discovered explains how EBV can remain in our body for so long, which may play a role in its later ability to cause cancer.
B lymphocytes typically spend their lives producing antibodies in response to infections — but, in the case of EBV, they are also the target of the viral attack.
Viruses are parasites and need to use the host cell's proteins and enzymes to copy itself. EBV uses the B lymphocytes to manufacture more virus. Once a virus replicates, the new viral particles escape from the host cell. Much of the time, they end up killing the cell, too. But EBV has found a way to keep the cells alive when it bursts forth.
The scientists found that EBV goes through several stages while infecting cells, and those phases force the body to make more B cells, lets the virus keep the cells alive, and allows it to live on quietly hidden in the B cells, which can survive in the body for decades in an immortalized state.
It all depends on stopping the cell's mitochondria — an organelle that produces energy and helps shut the cell down when stressed, infected, or old — from helping the cell die. EBV can stop that process, keeping the cell alive even when it's under attack.
Before an EBV virus infection becomes active, it manipulates the cell's chemical signals to produce lots of B cells to infect. Later in the active infection stage, the virus makes a protein called EBNA3A, which suppresses the normal cell-killing function of mitochondria. During the latent phase, EBV increases another protein called LMP, which activates NFkB, a family of proteins critical for the survival of the now-immortalized B cells.
Through these processes, EBV manages to create a pool of B cells to infect, keeps them from dying, and ensures their survival.
What's the Cancer Link, Then?
Interestingly, low LMP levels and high levels of B cell production — similar to the first phase of EBV infection — are associated with tumors caused by EBV. A previous study showed that EBV engineered to lack LMP completely was capable of forming B cell tumors in mice.
The scientists now know how EBV sets our bodies up to keep the virus safely hidden in B cells, and they believe the viral proteins LMP and EBNA3A active in that process may also be involved in EBV's cancer-causing mechanism.
Future studies into those proteins may figure out a way to prevent EBV from remaining in our cells and prevent EBV from changing from a latent virus to a cancer-causing virus.
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Cover image via National Cancer Institute
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