The virus behind glandular fever, also known as mononucleosis or kissing disease, seems to infect and reprogram immune cells in the body, priming some people to develop the autoimmune condition lupus.

Lupus, or systemic lupus erythematosus, occurs when the immune system becomes hyperactive, with sustained activity of immune cells called B-cells and T-cells leading to attacks on healthy tissues. This causes a variety of symptoms, including painful muscles and joints, rashes and extreme tiredness. What causes lupus isn’t well understood, but it probably involves an interplay of genetics, hormonal factors and environmental triggers, such as viruses and disturbances to our microbiome.

People with lupus – – tend to have relatively (EBV), which causes glandular fever. However, , usually without symptoms, while lupus affects around 5 million people worldwide.

To figure out how they might be linked, at Stanford University in California and his colleagues developed a single-cell RNA-sequencing platform called EBV-seq to find which B-cells – which produce antibodies to neutralise pathogens – are infected by EBV in people with lupus, and work out what genes are being expressed by these cells to produce RNA molecules.

In blood samples from 11 people with lupus, the researchers found that about 25 of every 10,000 sequenced B-cells were infected with EBV. In contrast, in 10 people without the condition, 0 to 3 of every 10,000 sequenced B-cells were infected with the virus.

Most of the infected cells were a type of B-cell called memory B-cells, which remember past pathogenic threats so they can trigger a faster response next time they crop up.

Free newsletter

Sign up to Health Check

Sign up to newsletter

Robinson and his colleagues have shown that these infected memory B-cells express genes called ZEB2 and TBX21, triggering a chain reaction that activates another type of immune cell, called helper T-cells, that recruit uninfected B-cells. This ramps up immune activity in a vicious cycle to a point at which it starts attacking the body.

Crucial to demonstrating EBV’s causal role in lupus was the finding that the virus appeared to prime memory B-cells to act this way by producing a protein called EBNA2, which bound to the ZEB2 and TBX21 genes, boosting their activity. “Our discovery is the mechanism by which this very common virus that infects 95 per cent of us, Epstein-Barr virus, basically causes lupus,” says Robinson.

As to why most people with EBV don’t develop lupus, Robinson thinks some people’s genetics predispose them to having B-cells that are more likely to mistakenly target healthy cells. “It’s EBV infection in the context of the genetic and environmental milieu that predisposes one to lupus that together results in them getting lupus,” he says.

Women have supercharged immune systems and we now know why

Being born with two X chromosomes brings a host of health benefits, and recognising this could lead to personalised medical treatments for men and women

“EBV isn’t necessarily likely to play a part in every case of lupus, because the mechanisms that are involved in expression of lupus are very varied, but in distinct patients, I’m sure it’s going to be a main contributor,” says at Harvard Medical School, who reported that in people with lupus more than 40 years ago.

A strong link was found between EBV and multiple sclerosis, another autoimmune condition, in 2022, and the new findings show how the virus could drive such disorders more broadly, says Robinson.

What’s more, they could explain why some CAR T-cell therapies­ have shown impressive results in clinical trials for lupus. These treatments, which involve genetically engineering someone’s T-cells to attack specific targets, were developed to treat blood cancers that arise when B-cells multiply out of control, and often deplete B-cells. “These CAR T-cell treatments seem to result in what we call long-term durable remission, where [lupus] patients are off all drugs, suggesting that they might even cure people. And we think it’s possible that they might achieve this by getting rid [of] or depleting the EBV-infected B-cells,” says Robinson.

A fresh understanding of tiredness reveals how to get your energy back

Radical new insights from the science of interoception – how the body senses its internal state – explain the real reasons we feel tired all the time, and how to re-energise

But the jury is still out on the therapies’ potential as a lupus treatment, says Tsokos, partly because, though levels of B-cells seem to drop in the blood of people given CAR T-cells, the cells often hide in bone marrow, and we don’t yet have data to show that all of them are being removed.

The work also supports the development of a vaccine against Epstein-Barr virus, which is transmitted by saliva, for potentially preventing a range of autoimmune conditions. “A vaccine has the potential to prevent EBV infection and could thereby prevent lupus in the future,” says Robinson, but he adds it wouldn’t ward off the condition in people who are already infected with EBV, because the B-cell reprogramming seems to happen early after infection.

Tsokos thinks the rollout of any EBV vaccine will come down to cost and how its benefits compare with any side effects, because you would probably need to vaccinate more than 1000 people to stop just a single case of lupus, he says.

Despite many decades of effort and numerous human trials, only one virus that is designed to kill cancers has ever been approved by regulators in the US and Europe. But a second could get the green light at the end of the month, after getting good results for treating melanoma, a particularly serious type of skin cancer.

A genetically modified herpes virus, called RP1, of 140 people with advanced melanoma for whom standard treatments had failed. The participants also took a drug called nivolumab, which is designed to boost the immune response to tumours.

In 30 per cent of those treated, tumours shrank, including those that were not injected. In half of these cases, the tumours disappeared altogether.

“Half the responders had complete responses, meaning the complete disappearance of all tumours,” says at the University of Southern California. “We’re very excited about these results.” The other options for treating people at this stage don’t work as well and have more serious side effects, he says.

A later-stage trial that will involve 400 people is now under way, but RP1 could be approved by the Food and Drug Administration (FDA) in the US for treating advanced melanoma in combination with nivolumab long before this trial finishes, In told 91av. “The FDA is supposed to give us a decision at the end of this month.”

It has been known for more than a century that viral infections can sometimes help treat cancers, but deliberately infecting people with “wild” viruses is very risky. In the 1990s, biologists began genetically modifying viruses to try making them better at treating cancers, but unable to harm healthy cells.

Free newsletter

Sign up to Health Check

Sign up to newsletter

These viruses are designed to work in two ways. Firstly, by directly infecting cancer cells and killing them by bursting them apart. Secondly, by triggering an immune response that targets all cancerous cells, wherever they are in the body.

For instance, a herpes simplex virus known as T-VEC, or Imlygic, was modified to make infected tumour cells release an immune-stimulating factor called GM-CSF, among other changes. In 2015, T-VEC was approved in the US and Europe for treating inoperable melanoma.

But T-VEC is not widely used, says In, in part because it was only tested on and approved for injecting into tumours in the skin. Most people with advanced melanoma have deeper tumours, he says.

We are finally improving prostate cancer diagnoses – here’s how

Cases of prostate cancer are surging alarmingly around the world. Thankfully, we are developing more accurate tests that can catch the condition early

With RP1, the decision was made to also try injecting it into deeper tumours. RP1 is a herpes simplex virus, like T-VEC, but has been improved in numerous ways. In particular, it makes tumour cells fuse with neighbouring cells, helping the virus to spread through tumours and boosting the immune response.

There have been no directly comparable trials of T-VEC and RP1, but RP1 is more likely to induce shrinking of all tumours, not just the injected ones, In says. “That indicates a more powerful systemic effect.”

Therefore, In expects RP1 to be much more widely used than T-VEC if it is approved. It will also provide a big boost to the whole idea of using cancer-killing viruses, he says. “I expect there will be a lot more interest.”