Viral infections and multiple sclerosis

The etiology and pathogenesis of MS is likely to involve multiple factors interacting with each other, and the role of infectious and viral agents is still under debate, however a consistent amount of studies suggests that some viruses are associated with the disease. The strongest documentation has come from the detection of viral nucleic acid or antigen or of an anti-viral antibody response in MS patients. A further step for the study of the mechanism viruses might be involved in can be made using in vitro and in vivo models. While in vitro models, based on glial and neural cell lines from various sources are widely used, in vivo animal models present challenges. Indeed neurotropic animal viruses are currently used to study demyelination in well-established models, but animal models of demyelination by human virus infection have only recently been developed, using animal gammaherpesviruses closely related to Epstein Barr virus (EBV), or using marmosets expressing the specific viral receptor for Human Herpesvirus 6 (HHV-6). The present review will illustrate the main potential mechanisms of MS pathogenesis possibly associated with viral infections and viruses currently used to study demyelination in animal models. Then the viruses most strongly linked with MS will be discussed, in the perspective that more than one virus might have a role, with varying degrees of interaction, contributing to MS heterogeneity.