Most people get infected with the Epstein-Barr virus, but only a minority become seriously ill.
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Recent studies present compelling evidence linking the Epstein-Barr virus (EBV) to the onset of multiple sclerosis (MS). A comprehensive analysis involving over 600,000 individuals indicates that EBV effectively commandeers immune cells, disrupting their function and activating specific genes that heighten the risk of developing MS.
This widespread virus infects most individuals during their lifetime, but severe complications are rare. Notably, it impacts a specific immune cell type called B cells, which are instrumental in producing antibodies. Dr. Kate Attfield from the University of Oxford states, “It’s evident that this virus resides within B cells, manipulating them for its advantage.”
Multiple sclerosis is an autoimmune disorder characterized by the immune system erroneously attacking healthy tissue. This involves another immune cell type, T cells, infiltrating the brain, generating significant damage, particularly to the fatty myelin sheaths surrounding neurons. MS currently affects approximately 2 million individuals worldwide, leading to diverse symptoms ranging from vision impairments to motor tremors.
For decades, scientists have suspected EBV’s involvement in MS; however, proving this link has been challenging, especially considering that over 90% of adults have experienced EBV infection, often causing infectious mononucleosis. A groundbreaking study conducted in 2022 with 10 million participants confirmed that individuals with a history of EBV infections face significantly higher risks of developing MS compared to those unexposed to the virus.
The pressing question remains: why do some people progress to MS? A January study illuminated potential genetic components, revealing that about 10% of individuals carry variations that predispose them to harbor greater amounts of EBV post-infection. These variants are associated with increased susceptibility to MS and other autoimmune disorders.
Research led by Yoshiaki Yasumi and his team at Yale University School of Medicine delved deeper into EBV’s effects. Analyzing data from 617,186 individuals from the UK Biobank and the US-based All of Us study, the researchers sequenced genomes from blood or saliva samples to detect EBV DNA, which often persists indefinitely in infected hosts.
In alignment with prior studies, it was found that a small percentage of individuals had substantially higher levels of EBV DNA. Alarmingly, just 1% of the participants accounted for 64% of the total EBV DNA detected.
Following this, genome-wide association studies identified 39 genomic regions linked to higher EBV DNA levels. Notably, approximately one-third of these variants were also associated with a heightened risk of developing MS and other severe conditions.
Focusing on B cells specifically, the researchers isolated approximately 471,000 B cells from 38 participants, discovering that 1,069 were infected with EBV. These infected B cells exhibited abnormal behavior, exhibiting high expression of genes linked to both EBV presence and MS risk, alongside activating immune signaling pathways that stimulate T cells, the very cells that contribute to MS’s neurodegenerative effects.
Dr. Ingrid Kockum of the Karolinska Institutet in Stockholm highlighted the importance of understanding the functions of these genetic variants linked to EBV and MS. The variation in outcomes suggests that the immune response might fluctuate the risk of MS. Dr. Kockum elaborates, “A robust antibody response may suppress viral load, which could consequently lower MS risk. Therefore, variants that undermine early antibody responses might correlate with both elevated EBV levels and MS susceptibility.”
Certain genetic alterations can potentially exacerbate immune responses, propelling individuals toward MS. Professor Attfield emphasizes that some patients’ immune systems may be less effective at managing EBV, leading not only to higher viral loads but also increasing MS risks. “Distinguishing between these factors remains complex,” she concludes.
Long-term, various research teams aspire to develop treatments for MS. There’s emerging promise in targeting immune cells that combat EBV, and preventative vaccines against EBV are also in the pipeline. However, Attfield advises caution, noting that a true understanding of MS progression is essential. Interventions aimed at EBV might prevent MS but the benefits when the disease is already advanced are less clear. “At that stage, EBV may no longer be a factor or could be critical to the condition,” she adds.
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Source: www.newscientist.com
