A specific human herpes virus may play a role in the progression of multiple sclerosis (MS) by inhibiting myelin repair after demyelination.
That’s the conclusion of a new study, published this month by researchers from the University of Rochester, that looked at the impact of human herpesvirus 6 (HHV-6) on oligodendrocyte progenitor cells (OPCs). These cells normally help offset demyelination by seeking out areas of demyelination in the body and replenishing myelin.
In the new study, a team of researchers led by senior author Margot Mayer-Proschel, PhD, argues that a protein emitted by latent HHV-6 disrupts OPCs, thus allowing demyelination to occur without the offsetting remyelinating function of OPCs.
This isn’t the first time HHV-6 has been linked to MS. In fact, scientists have suspected a connection since 2003, when another team of researchers from the University of Rochester Medical Center discovered that latent HHV-6 infection correlated with demyelination disorders. Initially, some thought HHV-6 might act as the trigger for MS. However, that has since been disproven, leaving the exact role of HHV-6 an open question.
HHV-6 infection is extremely common. Four out of five people will be exposed to the virus during childhood, though only about 1% of people will contract the virus congenitally.
In virtually all cases, HHV-6 eventually becomes latent, though it never leaves the body. Instead, the virus “hides” itself in the person’s genetic code, and expresses proteins, including one called U94A.
Mayer-Proschel and colleagues wondered if the latent virus could still do harm.
“The latency state has generally been considered to be benign,” the authors wrote. “However, serological data from MS patients showing increased prevalence of anti-U94A immunoglobulins and the presence of viral genome, transcripts, and antigen in tissue samples from patients with demyelinating disease in the absence of infectious virions prompted us to consider the impact of latent HHV-6A on OPC functions that are relevant for repair processes.”
To study the question, the researchers transplanted human OPCs into animal models. They found that whenever the protein U94A was expressed in an OPC, the OPC seemed to have limited ability to locate areas where demyelination was occurring.
“These findings show that, while in the process of hiding from the immune system, the virus produces a protein that has the potential to impair the normal ability of cells in the brain to repair damaged myelin,” Mayer-Proschel, an associate professor in the University of Rochester’s Department of Biomedical Genetics, said.
Thus, rather than triggering MS, HHV-6 might instead be a cause of disease progression in relapsing-remitting MS and other demyelination disorders.
Still, given the pervasiveness of HHV-6, the potential link with MS progression raises just as many questions as answers, such as how and when does latent HHV-6 begin to impact the disease, and if it matters whether a person contracted HHV-6 at birth or later in life.
“More research is needed to understand by which mechanisms the virus impedes the function of OPCs and what impact this has on the progression of these diseases,” Mayer-Proschel said in a press release. “But it is clear that HHV-6, while not necessarily the cause of demyelinating diseases, is limiting the ability of the brain to repair damage to myelin thereby potentially accelerating the progression of these diseases.”
The study, titled, “Expression of the Human Herpesvirus 6A Latency-Associated Transcript U94A Disrupts Human Oligodendrocyte Progenitor Migration,” was published online in this month.