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Debate over role of Eppstein-Barr virus in MS reinvigorated

Posted on behalf of Katherine Rowland.

Research on the possible contribution of Epstein-Barr virus (EBV) to Multiple Sclerosis (MS) has yielded discordant results. However, a new study on EBV and MS suggests that the association may be more “sophisticated” than thought.

MS is a multifactorial disease; its causes are many and include both genetic and environmental influences.

EBV is one of several identified infectious risk factors. “It’s not the only candidate,” says Jan Lünemann of the University of Zurich, “but it is by far the strongest candidate.”

A professor at the Institute of Experimental Immunology, Lünemann explains: “We know there is an epidemiological link between symptomatic EBV, or mononucleosis, and MS risk later in life. That is accepted in the field. The controversy is whether EBV drives the inflammation of the central nervous system associated with MS.”

The controversy also pertains to a brief, but contentious, history of inconsistent findings. In 2009, a group of Italian researchers released a provocative report in the Journal of Experimental Medicine offering evidence to suggest a strong connection between EBV infection and MS. However, subsequent attempts to replicate the findings did not establish a link.

According to Lünemann, the new study, published this week in the journal Neurology, “Reopens a debate that was heading towards a negative conclusion.”

Investigators at the Queen Mary University of London analysed post-mortem tissue samples from areas where MS damage had occurred. Using EBV-encoded RNA, the researchers found that even though the virus was not active, it was still releasing chemical messages affecting the body’s immune system.

“EBV is a very clever virus,” explains Ute-Christiane Meier, one of the study’s co-authors. “It was surprising to find it in the non-active, latent stage, in a less aggressive form.”

Meier admits that the role of a viral agent in MS is mired in controversy. “People have tried to pinpoint trendy viruses for decades.”

Although the research team identified latent EBV in 100% of their samples, the authors are quick to acknowledge more than 90% of the general population already carries the virus. The near-universality of EBV has both hindered and helped researchers’ efforts to understand its role in MS.

“EBV stands out,” says Alberto Ascherio, of the Harvard School of Public Health in Boston, Massachusetts. “It’s the only virus for which we’ve demonstrated that infection versus non-infection is related to MS risk.” However, Ascherio adds that that EBV does not have a direct effect.

“That’s not the picture. MS is obviously not a direct result of an overwhelming EBV or other viral infection, it’s connected to a more complicated immunologic response.”

And, according to Ascherio, the new study may help to make sense of some of the complications. “It may help to bridge the controversy between EBV and MS lesions.”

For Meier, who describes the virus as a “culprit at the scene of the crime,” the findings raise further questions about the persistence of EBV in the population, and how it has evolved ways to hide out in a non-active state. “It’s not in the interest of EBV to kill its host. It’s very manipulative. It wants to spread to as many other hosts as possible, and remain innate, otherwise its host wouldn’t survive, and neither would it.”

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