Aug 31, 2009
International Team Refutes Finding of Evidence of Epstein-Barr Virus in Brains of People with MS
Harvard investigators funded in part by the National MS Society, in collaboration with an international team, reported finding no evidence of Epstein-Barr virus infection in the brains of people with MS, refuting earlier studies claiming physical evidence of the virus in brain specimens. This study does not address other previous findings showing that people with high antibody levels against the virus or who have experienced infectious mononucleosis as a result of the virus are more susceptible to MS than the general population, and does not close the door on EBV as a possible risk factor for MS. Researchers Kevin C. O’Connor, PhD (a Society Career Transition Fellowship recipient), Simon N. Willis, PhD, and others report their findings in the journal Brain, published early online July 28, 2009.
Background on EBV and MS: Epstein-Barr virus is a herpesvirus known to cause infectious mononucleosis and other disorders. Most people in the general population have been exposed to the virus. After an initial infection EBV becomes latent or dormant, and can be reactivated at a later date. EBV infects B cells, the cells of the immune system that make antibodies. There is currently no vaccine that can protect against an initial infection by EBV, and no anti-viral medication that can fight the active infection or kill latent virus harbored in the body. This virus does not infect other species, so research on EBV can only be carried out in humans.
The cause of MS, an unpredictable immune-mediated disease that attacks the central nervous system, is unknown, but the disease is thought to occur when susceptible individuals encounter a triggering factor or factors in their environment. Several previous studies have suggested a possible link between EBV and MS, but other infectious agents have also been linked to MS, leading some researchers to suggest that the way the immune system responds to infections, rather than the infectious agent itself, may lead to the onset of MS. Previous examinations of MS brain tissue for signs of EBV have been mixed, some negative and some positive.
In 2006, National MS Society-supported investigators at Harvard and Kaiser Permanente showed evidence that individuals who had elevated antibody titers against EBV were twice as likely to develop multiple sclerosis up to 20 years later (Archives of Neurology). In 2007, investigators from Italy (Instituto Superiore di Sanita, Rome) and the United Kingdom reported finding traces of Epstein-Barr virus in postmortem brains examined from people with different forms of MS, finding evidence of EBV infection in immune cells (B cells and plasma cells) that had infiltrated the brain in 21 out of 22 brains (Journal of Experimental Medicine). And earlier this year, University of Buffalo researchers also reported on a link between EBV antibody levels and the loss of nerve tissue, and on a study exploring interactions between a person’s genes and EBV.
This study: The investigators conducted this study to try to shed better light on whether an EBV infection in the brain actually triggers or participates in MS activity, or whether the link with MS is less direct. They focused on trying to replicate previous findings of traces of EBV in brains of people with MS and EBV infection in immune cells that had infiltrated MS brain specimens, examining in some cases specimens from the same brains that had been used by the Italian investigators for their 2007 study. In total they examined multiple specimens from 24 MS brains.
The team used several different techniques to detect the presence of EBV, including PCR (polymerase chain reaction) to amplify very low signals and in situ hybridization, and also looked for the virus with a tissue staining technique (immunohistochemistry). Signs of EBV were absent from MS lesions, even those that contained B cells, the type of immune cell that harbors the virus. The team also looked at B cell follicles in or near the meninges, the membrane that encloses the brain, where the Italian investigators had reported striking evidence of the virus. They found low levels of EBV in only two of the 12 specimens of meninges examined.
The investigators conclude that EBV infection in the brain is rare in MS and unlikely to be directly involved in MS pathology in most cases.
Comment: This study raises doubts about the possibility that persistent Epstein-Barr virus infection in the brain plays a role in multiple sclerosis. It also draws attention to the fact that there remain some unresolved technical issues related to detecting the virus. This study does not negate other findings showing that people with high antibody titers to Epstein-Barr virus, or who have experienced infectious mononucleosis as a consequence of EBV, are more susceptible to MS than the general population, and does not close the door on EBV as a possible risk factor for MS.