And why out of all the people who have been infected with EBV do only a very small proportion go on to develop MS?

That's one of, uh, the central questions in the field.

I mean, EBV infection appears to be necessary but, uh, not sufficient to cause MS. Um, as said, more than 90% of people are infected worldwide with EBV, yet only around one in 500 or 1,000 in milder latitudes develops MS.

And this tells us that MS is, uh, resulting from the convergence of several risk factors rather than, than a single cause.

The first layer is genetics.

More than 200 genetic susceptibility variants have now been identified, the strongest effect coming from the HLA-DB1501 allele, which encodes for the HLA-DA2 haplotype, the molecule that presents antigens to CD4 T cells, but other risk alleles have been identified.

Many of these risk genes regulate immune function, and interestingly, several are directly influenced, kind of activated by the EBV transcription factor EBNA2.

And what are the main things that we still don't know about EBV and MS, and what do you think are the most important next steps for the field?