# Human herpesvirus 7 and the risk of developing multiple sclerosis

## TL;DR

This study finds that infection with human herpesvirus 7 increases the risk of developing multiple sclerosis, especially when combined with Epstein–Barr virus.

## Contribution

First large-scale study showing human herpesvirus 7 as a risk factor for multiple sclerosis and its synergistic interaction with Epstein–Barr virus.

## Key findings

- Human herpesvirus 7 infection is associated with a 2.2-fold increased risk of multiple sclerosis.
- A synergistic interaction exists between human herpesvirus 7 and Epstein–Barr virus in increasing multiple sclerosis risk.
- The association remains significant after adjusting for other herpesviruses like cytomegalovirus and human herpesvirus 6A.

## Abstract

Epstein–Barr virus is now regarded as the critical risk factor for multiple sclerosis. However, Cytomegalovirus and human herpesvirus 6A have also been associated with altered multiple sclerosis risk, suggesting a multifactorial aetiology. Here, we present the first large-scale study of the association between human herpesvirus 7 and the risk of developing multiple sclerosis. A nested case-control study was performed by crosslinking Swedish registries and biobanks, identifying blood samples from 981 cases who later developed multiple sclerosis and 1278 matched controls. Serological testing was performed with a multiplex immunoassay. The association between viral serostatus and the risk of developing multiple sclerosis was analysed with conditional logistic regression, calculating an odds ratio with 95% confidence interval. Interactions between antibodies against human herpesvirus 7 and the Epstein–Barr virus nuclear antigen 1 regarding multiple sclerosis risk were analysed on the additive scale. Serological evidence of human herpesvirus 7 infection was associated with a higher risk of developing multiple sclerosis: odds ratio = 2.2 (95% confidence interval = 1.8–2.7), P < 0.001. The results remained similar when adjusting for cytomegalovirus, Epstein–Barr virus and human herpesvirus 6A serostatus. Synergistic interactions between human herpesvirus 7 and Epstein–Barr virus nuclear antigen 1 seroreactivity were observed: attributable proportion due to interaction = 0.51 (95% confidence interval = 0.34–0.68). These results suggest that human herpesvirus 7 could be a contributing factor in multiple sclerosis aetiology.

Ingvarsson et al. report that serological evidence of infection with human herpes virus 7 is associated with a higher risk of developing multiple sclerosis. They also report a synergistic interaction between human herpes virus 7 and Epstein–Barr virus regarding the risk of developing multiple sclerosis, suggesting a mechanistic link.

Graphical Abstract