File photograph by Rose Lincoln/Harvard Staff Photographer


Epstein-Barr Virus implicated as a cause of MS

4 min read

Study followed subjects from health, through EBV infection, to MS

Researchers from the Harvard School of Public Health, Walter Reed Army
Institute of Research, and a team of collaborators have observed for
the first time that the risk of multiple sclerosis (MS) increases by
many folds following infection with the Epstein-Barr virus (EBV). This
finding implicates EBV as a contributory cause to multiple sclerosis.
The study was published in an advance online edition of the journal Annals
of Neurology
and will appear in a later print edition.

Hundred of thousands of individuals not infected with EBV were
followed up for several years through repeated blood samples
collections. Researchers were then able to determine the time when
individuals developed an EBV infection and its relation to MS onset.
“The recruitment of individuals before they were infected with EBV and
following up with them for several years is the critical methodological
aspect that makes this study qualitatively different from all previous
work,” said Alberto
, senior author of the study and professor of epidemiology
and nutrition at Harvard School of Public Health and professor of
medicine at Harvard Medical School.

MS is a chronic degenerative disease of the central nervous system.
Women are more likely than men to get the disease and it is the most
common neurologically disabling disease in young adults. Although
genetic predisposition plays an important role in determining
susceptibility, past studies have shown that environmental factors are
equally important.

EBV is a herpes virus and one of the most common human viruses
worldwide. Infection in early childhood is common and usually
asymptomatic. Late age at infection, however, often causes infectious
mononucleosis. In the U.S., upwards of 95% of adults are infected with
the virus, but free of symptoms. EBV has been associated with some types
of cancer and can cause serious complications when the immune system is
suppressed, for example, in transplant recipients. There is no
effective treatment for EBV.

This is the first study based on the longitudinal follow-up of
several thousand individuals who were not infected with EBV at the time
of recruitment. The study population was made up of active-duty US Army,
Navy, and Marines personnel who have at least one blood sample in the
Department of Defense Serum Repository. The electronic databases of the
Physical Disability Agencies of the US Army and Navy were then searched
for individuals whose records indicated a possible diagnosis of MS
reported between 1992 and 2004.

The researchers selected 305 individuals diagnosed with MS and who
had blood specimens collected before the date of their diagnosis. Two
controls for each case were then selected from the serum database and
matched by branch of service, sex, date of blood collection, and age at
time of blood collection.

The study found that MS risk is extremely low among
individuals not infected with EBV, but it increases sharply in the same
individuals following EBV infection.

“The observation that MS occurred only after EBV is a big step
forward,” said Alberto Ascherio. “Until now we knew that virtually all
MS patients are infected with EBV, but we could not exclude two
non-causal explanations for this finding: that EBV infection is a
consequence rather than a cause of MS, and that individuals who are EBV
negative could be genetically resistant to MS. Both of these
explanations are inconsistent with the present findings,” said Ascherio.

“The evidence is now sufficiently compelling to justify the
allocation of more resources to the development of interventions
targeting EBV infection, or the immune response to EBV infection, as
these may contribute to MS prevention,” he said.

The study was supported by a grant from the National Institute of
Neurological Disorders and Stroke