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. 2022 Oct 7:13:1028972.
doi: 10.3389/fimmu.2022.1028972. eCollection 2022.

Epstein-Barr virus, interleukin-10 and multiple sclerosis: A ménage à trois

Günther Schönrich  1 , Mohammed O Abdelaziz  1 , Martin J Raftery  1   2
Affiliations

Epstein-Barr virus, interleukin-10 and multiple sclerosis: A ménage à trois

Günther Schönrich et al. Front Immunol. .

Abstract

Multiple Sclerosis (MS) is an autoimmune disease that is characterized by inflammation and demyelination of nerve cells. There is strong evidence that Epstein-Barr virus (EBV), a human herpesvirus infecting B cells, greatly increases the risk of subsequent MS. Intriguingly, EBV not only induces human interleukin-10 but also encodes a homologue of this molecule, which is a key anti-inflammatory cytokine of the immune system. Although EBV-encoded IL-10 (ebvIL-10) has a high amino acid identity with its cellular counterpart (cIL-10), it shows more restricted and partially weaker functionality. We propose that both EBV-induced cIL-10 and ebvIL-10 act in a temporally and functionally coordinated manner helping the pathogen to establish latency in B cells and, at the same time, to balance the function of antiviral T cells. As a result, the EBV load persisting in the immune system is kept at a constant but individually different level (set point). During this immunological tug of war between virus and host, however, MS can be induced as collateral damage if the set point is too high. Here, we discuss a possible role of ebvIL-10 and EBV-induced cIL-10 in EBV-driven pathogenesis of MS.

Keywords: IL-10; antiviral immune responses; multiple sclerosis; viral IL-10; viral immune evasion; virus-induced immunopathogenesis; viruses.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Regulation of the EBV load by IL-10. After transmission, EBV infects naïve B cells, which are then reprogrammed and replenish the pool of latently EBV-infected memory B cells. Occasionally, EBV reactivates and lytically infected plasma cells produce new virus particles, which infect new naïve B cells completing the viral life cycle. After reinfection, epithelial cells of the oropharynx shed viral particles into the saliva, which passes EBV on to new individuals. Importantly, the coordinated action of EBV-induced cIL-10 and ebvIL-10 regulates the individual set point of the EBV load not only by reprogramming EBV-infected naïve B cells but also by regulating the activity of antiviral T cells that eliminate newly infected B cells.
Figure 2
Figure 2
Link between EBV load, risk for MS development, and EBV transmission. At a high set point of the EBV load (left side), reactivation of EBV in latently infected memory B cells and release of infectious EBV particles occurs frequently in lymphoid tissue. This may allow not only persistent oral shedding with high EBV transmission but also facilitate pathogenic B–T cell interactions thereby drastically increasing the risk for pathogenic T ell responses that initiate and drive MS through molecular mimicry. The latter occurs when B cells present EBV-derived peptides that are similar to self-peptides found in CNS antigens. At a low set point (right side), however, EBV reactivates only rarely resulting in inefficient EBV transmission due to reduced oral shedding and only a low risk for MS.
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