- Epstein Barr virus infection is an established risk factor for MS
- The potential role of other viruses, VZV, CMV and HHV-6, in risk of MS was investigated
- Of these, only HHV-6 was found to increase risk of the first clinical signs of myelin loss.
Multiple sclerosis (MS) is characterised by the loss of the insulating layer around the nerves, called myelin, that helps conduct signals to and from the brain and spinal cord, and the rest of the body.
Previous infection with Epstein-Barr virus (EBV) is well-established as a risk factor for the development of MS.
However, the role of other viruses, and their interplay with EBV, is not clear.
A new Australian study published in the European Journal of Neurology, has examined the role of additional viruses in the risk of MS, against the backdrop of EBV infection.
More specifically, the study examined other viruses as risk factors for the precursor to MS: a first clinical diagnosis of myelin loss (demyelination) in the brain and spinal cord, or FCD.
Other viruses with possible MS association
In addition to EBV, human herpesvirus 6 (HHV-6) is another herpes virus that has been repeatedly investigated as a risk factor for MS, with inconsistent findings.
There are two forms of HHV-6, with the HHV-6B form responsible for a common infection in infants called roseola, or “sixth disease”; but both variants are known to infect nerve cells.
Researchers have also investigated other common viruses, like the varicella-zoster virus (VZV; the cause of chickenpox and shingles). The link between VZV and MS is still uncertain.
Cytomegalovirus (CMV) infection, like EBV, can manifest as infectious mononucleosis and be mild or show no symptoms. Past CMV infection may be associated with a reduced risk of MS in some populations.
What did the researchers do?
The researchers looked for signs of infection with these viruses in people with a first clinical diagnosis of demyelination (204 people), compared to healthy controls matched for age, sex and study region (215 people).
They collected blood samples from people as part of the Ausimmune study, which is funded by MS Australia.
Viral load (DNA) of EBV, VZV and HHV-6 in the blood; as well as levels of antibodies to EBV, VZV, HHV-6 and CMV in serum were measured.
Analysis was conducted to determine whether these viruses were independently associated with the risk of a first demyelinating event, after taking EBV infection and other potential risk factors into account.
What did the researchers find?
Of the various viruses tested, only HHV-6 viral load was associated with a first demyelinating event, in addition to EBV.
More complex statistical modelling that accounted for educational category, serum vitamin D levels, smoking, and EBV status, also found only HHV-6-DNA load to be associated with FCD.
Interestingly, the researchers also found that, in people who carry a specific MS risk gene, higher antibodies to CMV reduced the risk of first clinical demyelination.
What does this mean for understanding MS?
These findings highlight the possible importance of HHV-6 as a risk factor for the onset of MS.
This aligns with laboratory studies linking HHV-6 to MS.
Antibodies to HHV-6 have been detected in the cerebrospinal fluid (surrounding the brain and spinal cord) in MS.
In laboratory models of MS, the addition of HHV-6 virus accelerated the disease and concentrated in areas of brain injury.
HHV-6 has also been shown to slow down the repair of myelin and block the movement of myelin-producing cells.
Overall, this study adds to the evidence on the possible role of human herpesviruses in the onset of MS.