Viruses and Multiple Sclerosis
Jussi Oskari Virtanen and Steve Jacobson
Pages 528-544 (17)
Multiple sclerosis (MS) is a heterogeneous disease that develops as an interplay between the immune system
and environmental stimuli in genetically susceptible individuals. There is increasing evidence that viruses may play a role
in MS pathogenesis acting as these environmental triggers. However, it is not known if any single virus is causal, or rather
several viruses can act as triggers in disease development. Here, we review the association of different viruses to MS with
an emphasis on two herpesviruses, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). These two agents have
generated the most impact during recent years as possible co-factors in MS disease development. The strongest argument
for association of EBV with MS comes from the link between symptomatic infectious mononucleosis and MS and from
seroepidemiological studies. In contrast to EBV, HHV-6 has been found significantly more often in MS plaques than in
MS normal appearing white matter or non-MS brains and HHV-6 re-activation has been reported during MS clinical
relapses. In this review we also suggest new strategies, including the development of new infectious animal models of MS
and antiviral MS clinical trials, to elucidate roles of different viruses in the pathogenesis of this disease. Furthermore, we
introduce the idea of using unbiased sequence-independent pathogen discovery methodologies, such as next generation
sequencing, to study MS brain tissue or body fluids for detection of known viral sequences or potential novel viral agents.
Multiple sclerosis, human herpesvirus 6, Epstein-Barr virus.
Neuroimmunology Branch, NINDS, NIH, Building 10, Room 5C-103, 9000 Rockville Pike, Bethesda 20892, MD, USA.