The Epstein-Barr virus (EBV), which resides silently inside the bodies of 19 out of 20 Americans, is directly responsible for commandeering what starts out as a minuscule number of immune cells to go rogue and persuade far more of their fellow immune cells to launch a widespread assault on the body’s tissues, the scientists have shown.

“This is the single most impactful finding to emerge from my lab in my entire career,” said William Robinson, MD, PhD, a professor of immunology and rheumatology and the study’s senior author. “We think it applies to 100% of lupus cases.”

Transmitted in saliva, EBV infection typically occurs in childhood, from sharing a spoon with or drinking from the same glass as a sibling or a friend, or maybe during our teen years, from exchanging a kiss. EBV can cause mononucleosis, “the kissing disease,” which begins with a fever that subsides but lapses into a profound fatigue that can persist for months.

Oddly, about 20% of the B cells in our bodies are autoreactive. They target antigens belonging to our own tissues — not by design, but due to the random way B-cell diversity comes about: through sloppy replication, apparently engineered by evolution to ensure diversification. Fortunately, these B cells are typically in a dopey state of inertia, and they pretty much leave our tissues alone.

But at times, somnolent autoreactive B cells become activated, take aim at our own tissues and instigate one of the disorders collectively called autoimmunity. Some awakened autoreactive B cells crank out antibodies that bind to proteins and DNA inside the nuclei of our cells. Such activated “antinuclear antibodies” — the hallmark of lupus — trigger damage to tissues randomly distributed throughout the body, because virtually all our body’s cells have nuclei.

It’s known that the latent EBV, despite its near-total inactivity, nonetheless occasionally nudges the B cell it’s been snoozing in to produce a single viral protein, EBNA2. The researchers showed that this protein acts as a molecular switch — in geneticists’ language a “transcription factor” — activating a battery of genes in the B cell’s genome that had previously been at rest. At least two of the human genes switched on by EBNA2 are recipes for proteins that are, themselves, transcription factors that turn on a variety of other pro-inflammatory human genes.

Robinson said he suspects that this cascade of EBV-generated self-targeting B-cell activation might extend beyond lupus to other autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and Crohn’s disease, where hints of EBV-initiated EBNA2 activity have been observed.

Many companies are working on an EBV vaccine, and clinical trials of such a vaccine are underway. But that vaccine would have to be given soon after birth, Robinson noted, as such vaccines are unable to rid an already-infected person of the virus.