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 nonuniform, 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.

The aliens inside human DNA: HERV-W/MSRV/syncytin-1 endogenous retroviruses and neurodegeneration

“…With respect to HHV-6, meta-analyses provided some support for a link between HHV-6 and MS, but none showed causative relationships, and findings across the field are non-uniform [52]. Since we found significant increases of the expression of HERV-W in Figure 4.…”

“…This is particularly important for HHV-6 studies, as the vast majority of reports have detected virus DNA, and the need for studies to examine antigen and virus mRNA expression in MS and control brains to delineate the relationship between latent and active virus and MS has been emphasized [52]. By evaluating two different transcripts for each virus (MSRV/HERV-W env and pol, HHV-6 U94/rep, which maintains the latent state, and DNA-pol, indicative of actively replicating virus), we found that MSRV/HERV-W was expressed actively in human brains and activated strongly in MS patients (up to the protein level), while there were no significant differences between these MS patients and controls for HHV-6 presence/replication at the brain or PBMC level [32].…”

“…Among them, there were some members of the family of Herpesviridae, such as the human herpesvirus 6 (HHV-6) [52], and the EpsteinBarr virus (EBV) [53], along with HERV-W/MSRV/syncytin-1 [16,50,54].…”

The Secret Lives of Human Herpes Virus 6 (HHV-6)

“…I admit that this point of view is still considered controversial by many, but with regard to MS, renowned NIH Infectious Disease Expert Steve Jacobson has commented that "Ultimately, the only way to demonstrate the involvement, or lack thereof, of HHV-6 or other herpesviruses in this disease is through a controlled trial of an efficacious antiviral drug. " [14], which unfortunately has not happened yet. Equally unfortunately, citations of this body of work have virtually disappeared from the literature.…”

The Role of HTLV-1 in Alteration of Immune Regulation Through Regulatory T Cell Dysfunction and Exosomal Manipulation

“…Neuromyelitis optica (NMO), acute disseminating encephalomyelitis (ADEM), transverse myelitis (TM), and MS similarly involve inflammatory infiltrates and demyelination, but are instead thought to be autoimmune in nature. It has been suggested that MS develops after an initial viral insult, which has been supported by 9 animal studies in which viral infection worsens the course of experimental autoimmune encephalomyelitis (EAE) (Kakalacheva et al, 2011;Leibovitch and Jacobson, 2014) ( Leibovitch et al, 2013).…”