Several human herpesvirus (HHV) variants have been suggested to be complicit in the etiology of multiple sclerosis (MS). However, direct evidence of HHV involvement has been difficult and controversial due to the shortage of serological methods that can distinguish between the two main viruses thought to play a major pathological role—HHV-6A and HHV-6B. Yet now, researchers at Karolinska Institute have developed a new method to separate between the two viral strains.
Amazingly, by analyzing antibodies in the blood against the most divergent proteins of HHV-6A and 6B, the researchers were able to show that MS-patients carry HHV-6A to a greater extent than healthy individuals. These new findings—published recently in Frontiers in Immunology through an article titled “Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis”—point to a role for HHV-6A in the development of MS.
“This is a big breakthrough for both the MS and herpes virus research,” explained senior study investigator Anna Fogdell-Hahn, PhD, associate professor in the department of clinical neuroscience at the Karolinska Institute. “For one, it supports the theory that HHV-6A could be a contributing factor to the development of MS. On top of that, we are now able, with this new method, to find out how common these two different types of HHV-6 are, something we haven’t been able to do previously.”
MS is an autoimmune disease that affects the central nervous system. The cause of the disease is unclear, but one plausible explanation is a virus tricks the immune system to attack the body’s own tissue. Human Herpesvirus 6 (HHV-6) has previously been associated with MS, but in those studies, it wasn’t possible to distinguish between 6A and 6B. Through virus isolation from ill individuals, researchers have been able to show that HHV-6B can cause mild conditions such as roseola in children, but it has been unclear if HHV-6A is the cause of any disease.
Interestingly, estimates suggest as many as 80% of all children are infected with the HHV-6 virus before two years of age, and many also carry protection in the form of antibodies against this particular virus for the rest of their lives. But since it hasn’t been possible to tell the two variants apart post-infection, it has been difficult to say whether HHV-6A or B is a risk factor for MS.
In the current study, however, the researchers were able to distinguish between the A and B virus by analyzing antibodies in the blood against the proteins—immediate-early protein 1A and 1B (IE1A and IE1B)—that diverge the most between the two viruses.
The research team compared antibody levels in blood samples of some 8,700 MS-patients against more than 7,200 healthy people whose gender, date of birth, date of a blood sample, and other factors matched those with MS. They concluded that people with MS had a 55% higher risk of carrying antibodies against the HHV-6A protein than the control group. In a sub-group of almost 500 people, whose blood samples were drawn before the onset of the disease, the risk of developing MS in the future was more than doubled if they had a 6A viral infection.
Intriguingly, the younger the people were when the virus was first discovered in the blood, the higher the risk was of developing MS in the future. HHV-6B, on the other hand, was not positively associated with MS. Instead MS-patients had lower levels of antibodies toward IE1B than those without MS.
Antibodies toward Epstein-Barr virus (EBV), another herpes virus that is also associated with MS, were analyzed with the same method and the researchers were able to show that individuals affected with both viruses had an even greater risk of MS. This indicates that several virus infections could be acting jointly to increase the risk of MS.
“Both HHV-6A and 6B can infect our brain cells, but they do it in slightly different ways. Therefore, it is now interesting to go forward and attempt to map out exactly how the viruses could affect the onset of MS,” concluded Fogdell-Hahn.