Epstein-Barr Virus and Certain Genes Interact in Ways That Can Promote MS, Study Finds

Interaction between various Epstein-Barr virus traits and the composition of certain genes affects the risk of developing multiple sclerosis (MS), a study reports.

The study, “The interaction of Multiple Sclerosis risk loci with Epstein-Barr virus phenotypes implicates the virus in pathogenesis,” was published in the journal Nature Scientific Reports.

At present, slight variations of the same gene — known as single-nucleotide polymorphisms, or SNPs — at more than 200 gene locations have been linked to a higher risk of developing MS. Most of these genes are particularly active in immune cells.

However, the status of a person’s immune system plays a key role in the real-life effect that a person’s genetics has in MS development.

Previous studies suggest that B-cells (a type of immune cells implicated in MS) infected with the Epstein-Barr virus (EBV, a common form of the herpes virus) contributes to this disease’s onset.

B-cells infected with EBV can become immortalized — a status whereby cells avoid natural cell death and keep proliferating. In the development of MS, immortalized cells escape immune regulation by other immune system cells, leading to attacks on myelin, the protective coating on nerve cells in the central nervous system (brain and spinal cord).

Apart from the presence of EBV-infected B-cells, the number of DNA copies of EBV within B-cells is thought to also influence MS development.

Furthermore, many MS-associated genetic variants (differences in the DNA sequence between individuals) are linked to altered activity in EBV-infected B-cells, supporting evidence of an association between MS and EBV infection.

Here, the researchers’ goal was to determine if the presence of SNPs (variations of a given gene) associated with a greater MS risk could in fact influence the behavior and action of EBV.

EBV traits that investigators looked at included the number of the virus’ DNA copies within infected B-cells, and the expression of viral microRNAs, tiny molecules that can lower or silence the activity of certain genes.

Researchers found that the number of EBV DNA copies was affected by the expression of MS risk genes, and that while many gene SNPs were related to EBV DNA copy number, their influence varied among different SNPs.

They also observed that two EBV microRNAs, identified as miRNA BART4-3p and BART3-5p, were strongly linked to EBV DNA copy number and different MS risk SNPs.

One MS risk SNP in particular, defined as rs7260482, had a strong association with viral DNA copy number, the expression of BART4-3p and BART3-5p microRNAs, and the expression of the poliovirus receptor (PVR) gene in the host.

These results “are consistent with an EBV susceptibility signature contributing to risk of developing MS,” the researchers wrote.

The data obtained, they added, “support the hypothesis that EBV DNA copy number is correlated with expression of MS risk genes, associated with risk variants, and affected by these in a manner suggesting that targeting EBV DNA copy number would reduce EBV pathogenesis [development] in MS.”

Although no treatments “specifically targeting EBV” are currently available, the researchers also suggested that the effectiveness of immune therapies for MS “may substantially improve if they are combined with EBV therapies.”