“Mono” viruses increase the risk of MS and cancer for some people. 22 genes suggest why.

Approximately 90% of people will become infected with the Epstein-Barr virus at some point in their lives. In most cases, the virus causes a mild, transient illness or no symptoms at all. However, for some people, Epstein Barr may ultimately contribute to the development of chronic diseases such as lupus or multiple sclerosis, or cancer.

Now, a new study has uncovered 22 human genes that may increase the likelihood that Epstein-Barr infection progresses to chronic disease.

Researchers cannot yet say for sure whether these genes directly make the Epstein-Barr virus more dangerous, or whether they are part of an underlying immune suppression that allows the virus to persist in the body at higher than normal levels. But Jill Hollenbach, a professor of neurology at the University of California, San Francisco, who was not involved in the study, said the new study should be a starting point.

you may like

“My lab is already investigating the results and thinking about what we can learn from them and what other research avenues they might suggest,” Hollenbach told Live Science. Hollenbach wrote a commentary on the new study, published January 18 in the journal Nature.

nearly 20 genes

Epstein-Barr virus can cause mononucleosis, better known as mono, a temporary illness known for causing extreme fatigue. However, even after the mono-symptoms disappear, the virus remains dormant in the body, primarily in the immune system’s B cells, which remember and defend against certain bacteria.

For most people, this potential Epstein-Barr virus does not pose a problem. But in other people, the virus persists at higher, more active levels. In these cases, there is an increased risk of certain nasopharyngeal cancers and lymphomas, which can lead to autoimmune diseases such as multiple sclerosis. Chronic and active Epstein Barr has also been linked to heart and lung disease.

To understand why only some people seem to experience these chronic effects, Ryan Dinsa and colleagues at Baylor College of Medicine turned to an as-yet-unexplored source: the human DNA biobank. These biobanks collect complete genetic sequence data and health records for hundreds of thousands of individuals. When we sequence the human genome, we also scoop up the DNA of viruses that happen to be present inside cells.

“Typically, when we analyze human genome sequence data, we ignore reads that don’t map back to the human reference genome; we just kind of throw them away,” Dhindsa told Live Science. “Now we thought we’d take a look at the reads that we would normally throw away and see if we could recover the viral DNA.”

Researchers combed through neglected Epstein-Barr sequences from 750,000 people in the UK Biobank and the National Institutes of Health’s All of Us biobank and were able to identify individuals (about 11% of the total) with very high levels of Epstein-Barr DNA. They found that these high levels of viral DNA were associated with health conditions previously associated with Epstein Barr, including diseases such as spleen and Hodgkin lymphoma.

The presence of viral DNA was also associated with conditions thought to be associated with Epstein-Barr, including rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), and lupus, although this is not conclusive. Other associations in the data reinforce even less well-studied connections, including links between Epstein-Barr and heart disease, kidney failure, stroke and depressive episodes.

you may like

Additionally, researchers found that it is linked to 22 genes that are likely to be present in someone with 11% of patients with chronic Epstein-Barr disease. Many of these genes are located in a region of the genome called the human leukocyte antigen (HLA) locus, which is known to encode immune cells that present antigens (foreign molecules that trigger an immune response) to other immune cells.

“These variants appear to have changed the way an individual’s immune response actually presents the Epstein-Barr virus to the immune system,” Dhindsa said, which may have made it harder for the body to suppress the virus’s replication. However, the data only point to an association between these genes and persistent infection, and further research is needed to prove a causal relationship.

Researchers also observed mutations in genes that regulate the immune system in people with high levels of Epstein-Barr virus. One of these, the SLAMF7 gene, encodes a cell surface protein that normally helps the immune system’s natural killer cells attack tumors. The other, called CTLA4, codes for a receptor on T cells that prevents the immune system from attacking the body.

“They found some very interesting results,” Hollenback said.

She and her team are now interested in looking more deeply into the mechanisms that link genetic variation and the immune response to Epstein-Barr. Meanwhile, Dhindsa and his colleagues are interested in using the biobank data to explore other viruses that have long-term effects on human health. Examples include the oncogenic viruses Merkel cell polyomavirus and human T-cell lymphotropic virus type 1.

The researchers are also keen to extend their method to a more diverse global dataset of human genes. While the All of Us dataset includes participants from a variety of backgrounds, the UK Biobank is primarily comprised of people of European descent.

“Future studies should be able to examine genetic differences across more representative samples,” he said.