MS Risk Linked to Herpes Virus 6A and Not More Common 6B, Study Suggests

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by Ana Pena PhD |

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Ocrevus and infection risk

Human herpesvirus 6A (HHV-6A), but not a widespread variant of the virus called HHV-6B, could be one of the root causes of multiple sclerosis (MS), new research suggests.

Compared to healthy people, those with MS show greater numbers of antibodies to HHV-6A viruses, reflecting greater exposure to this type of infection and suggesting a link to this disease.

The study reporting these findings, “Increased serological response against human herpesvirus 6A is associated with risk for multiple sclerosis,” was published in the journal Frontiers in Immunology.

While the origin of MS remains unclear, research has proposed that viral infections by HHV-6 could be one of its causes.

The hypothesis is that the virus is able to mislead the immune system into attacking the body’s own tissues, damaging the brain and spinal cord. However, it has been impossible to say which specific type of the virus — 6A or 6B — is responsible for such risk.

HHV-6B is a very common virus acquired early in life. About 80% of all children are estimated to be infected before the age of 2. In children, HHV-6B can cause relatively mild conditions such as roseola, an illness marked by days of high fever, rashes, and, in some cases, febrile seizures.

Less is known about the consequences of HHV-6A, although this specific variant has been linked with MS.

Upon exposure to HHV-6, a person’s immune system raises antibodies against specific viral proteins, which help to protect them against the virus for the rest of their lives. The presence of these specific antibodies can be tested in blood samples to find who’s been exposed to the virus.

As HHV-6A and HHV-6B are extremely similar, it has not been possible to date to determine which of these herpes viruses the antibodies are reacting against when a person tests positive for this viral infection through a blood test.

Scientists at the Karolinska Institutet in Sweden devised a way to overcome this problem.

They were able to distinguish between 6A and 6B types by measuring antibodies in the blood that recognize the proteins that diverge most between the two viruses — called immediate early protein 1A and 1B (IE1A and IE1B).

Researchers compared antibody levels in blood samples of 8,742 people with MS and 7,215 healthy people, all in Sweden and matched for gender, date of birth, and other factors.

Results showed that MS patients had a 55% higher risk of carrying antibodies against HHV-6A than healthy people.

Further analysis in a group of 478 patients whose blood samples were collected before the onset of MS showed that viral infection by HHV-6A more than doubled a person’s risk of developing MS later on.

Researchers also saw that the younger the age at which patients tested positive for the HHV-6A virus, the higher the risk of MS.

In contrast, carrying antibodies against HHV-6B was not associated with MS development. In fact, MS patients tended to have lower amounts of antibodies against this type of virus than people without this disease.

“This is a big breakthrough for both the MS and herpes virus research,” Anna Fogdell-Hahn, an associate professor at Karolinska and one of the study’s senior authors, said in a news story.

“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,” Fogdell-Hahn added.

Infection by another herpes virus, called Epstein-Barr virus (EBV) and best known as the cause of mononucleosis, also has been proposed as a risk factor for MS.

Researchers analyzed antibodies against EBV, and observed that individuals affected with both viruses — EBV and HHV-6A — had an even higher risk of developing MS. This indicates that multiple viral infections can act together to raise a person’s susceptibility to the disease.

“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,” Fogdell-Hahn said.

A cause-effect relationship between the virus and MS, however, is not by any means established, and more studies are needed, the team emphasized.

For more information about this research, the Karolinska Institutet posted a video that can be viewed using this link.

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