Evidence linking HHV-6 with multiple sclerosis: an update

Abstract

Following reports of elevated antiviral antibodies in MS patient sera and viral DNA detection in MS plaques nearly two decades ago, the neurovirology community has actively explored how herpesviruses such as HHV-6 might be involved in MS disease pathogenesis. Though findings across the field are non-uniform, an emerging consensus of viral correlates with disease course and evidence of HHV-6-specific immune responses in the CNS provide compelling evidence for a role, direct or indirect, of this virus in MS. Ultimately, the only way to demonstrate the involvement, or lack thereof, of HHV-6 or other herpesviruses in this disease is through a controlled clinical trial of an efficacious antiviral drug.

Figure 1

HHV-6 expression is detectable by immunohistochemistry in a periventricular MS lesion (A–E), but not in the normal appearing white matter (F). Red: HHV-6 gp116. MS lesions were obtained from a subset of patient material previously reported [14].

Figure 2

A complex interplay between genetics, immune response and viral infections (such as HHV-6) influences the development of MS. Genetics have been implicated in the susceptibility to the disease, as well as in the response to antiviral therapy. Under certain inflammatory conditions, potentially in genetically susceptible individuals, the latency and persistence of herpesviruses may result in a dysregulated infection. Anti-viral immune responses in the periphery and CNS of MS patients suggest that a dysregulated viral infection is a key component of the disease. Adapted from Owens, Bennet. 2012 Mult Scler.