Stanford-led researchers report evidence that the Epstein‑Barr virus (EBV) may underlie virtually every case of systemic lupus erythematosus (SLE). Published in Science Translational Medicine in 2025, the study found markedly higher rates of EBV infection in specific B‑cell populations from people with lupus compared with healthy controls. In laboratory tests, EBV-infected B cells were reprogrammed to activate pro‑inflammatory genes, a change the authors say can drive systemic autoimmune responses. The team argues these results provide the strongest mechanistic link yet between a common human virus and lupus onset.
Key takeaways
- The study, led by Stanford immunologists and published in Sci. Transl. Med. (2025), reports EBV infects about 1 in 400 B cells in people with lupus — roughly 25 times the rate found in healthy donors.
- Researchers used a targeted sequencing method to detect EBV within circulating B cells and showed enrichment particularly in memory B‑cell subsets linked to rapid immune responses.
- In vitro, EBV infection shifted latent B cells into a pro‑inflammatory transcriptional state, activating genes that could sustain systemic autoimmunity.
- William Robinson, head of the lab, described the result as the most consequential from his group and suggested the mechanism may apply broadly to lupus cases.
- The findings align with clinical success of B‑cell–directed immunotherapies that induce remission-like responses in some SLE trials.
- Authors note potential wider relevance to other EBV‑associated autoimmune conditions including multiple sclerosis and post‑viral syndromes such as long COVID and ME/CFS.
Background
Epstein‑Barr virus is one of the most ubiquitous human viruses; most adults worldwide have been infected and the virus typically persists in a latent state with few symptoms. Historically, EBV has been suspected in a range of autoimmune and malignant conditions because of its tropism for B lymphocytes and its capacity to alter host gene expression. Systemic lupus erythematosus, a chronic autoimmune disease described in medical literature since the 19th century and with mentions as early as 850 CE, remains clinically heterogeneous and without a single established cause or cure.
Researchers have long grappled with why only a small fraction of EBV‑infected people develop lupus despite near‑universal exposure. Proposed contributing factors include host genetics, hormonal influences, environmental triggers and infections. The difficulty in resolving EBV’s role has been technical: the virus can hide inside B cells at very low abundance, making detection and cell‑specific analysis challenging. The Stanford team set out to overcome that limitation with a refined sequencing approach targeting viral reads inside single‑cell B‑cell profiles.
Main event
The investigators analyzed blood samples from people diagnosed with SLE and matched healthy controls. Using a sequencing pipeline optimized to capture EBV sequences inside B cells, they identified infected cells and compared their frequency and transcriptional programs between groups. In SLE patients, EBV‑positive B cells were far more common — about 1 in 400 B cells carried viral signal, versus roughly 1 in 10,000 in controls — and the infected cells were disproportionately found among memory B cells.
In laboratory cultures, introduction or reactivation of EBV in latent B cells triggered a transcriptional switch: genes associated with inflammation and antigen presentation were upregulated while some regulatory pathways were suppressed. The authors interpret this as a plausible cellular route by which an otherwise quiescent virus can convert specific B cells into drivers of systemic autoimmunity. The work combines viral sequencing, single‑cell transcriptomics and functional assays to link viral presence with altered B‑cell behavior.
Senior figures on the paper emphasized both the technical advance and the biological interpretation. Lead immunologist Shady Younis and colleagues present these data as a mechanistic bridge connecting EBV infection to SLE pathology, while William Robinson characterized the finding as the most impactful outcome from his laboratory to date. Outside experts acknowledged the significance of the data but urged replication and cautious interpretation of claims that EBV explains all lupus cases.
Analysis & implications
If EBV can reprogram memory B cells toward a pro‑inflammatory state, the virus provides a coherent explanation for several features of lupus: its relapsing‑remitting flares, the central role of B cells and antibodies in disease, and why targeting B cells can produce clinical improvement. A unifying viral trigger would reframe prevention and treatment strategies toward antiviral or vaccine approaches in addition to existing immunomodulation.
Translational implications are substantial but require careful validation. A vaccine or therapeutics that prevent EBV infection or limit its reactivation in B cells could, in principle, reduce the incidence or severity of lupus, but population‑level measures must weigh EBV’s ubiquity and mostly benign course in most people. The work may also inform why some B‑cell‑targeting therapies produce durable remissions: removing or replacing the misprogrammed B‑cell compartment interrupts a viral‑driven disease engine.
At the same time, the study does not immediately change clinical care. Confirmatory studies across diverse populations, longitudinal sampling to show causality over time, and mapping of viral strain differences or host genetic susceptibilities are needed. Policy and public‑health responses — including any vaccine deployment — would depend on replication, safety profiling, and demonstration that interrupting EBV alters lupus incidence or outcomes.
Comparison & data
| Group | EBV‑infected B cells (approx.) | Share of B cells (%) |
|---|---|---|
| People with lupus (SLE) | 1 in 400 | 0.25% |
| Healthy individuals | 1 in 10,000 | 0.01% |
The table highlights the order‑of‑magnitude difference the authors report: infected B cells are roughly 25 times more common in the SLE cohort than in controls. While percentages are small in absolute terms, infected cells concentrated in memory subsets could exert outsized effects by rapidly producing autoreactive antibodies and sustaining inflammatory circuits. The sequencing approach enabled detection of these rare infected cells, addressing a prior technical barrier to evaluating EBV’s role.
Reactions & quotes
Several scientists welcomed the technical advance and the potential explanatory power of the findings, while underscoring the need for independent replication and cautious claims about universality.
“This is the single most impactful finding to emerge from my lab in my entire career.”
William Robinson, Stanford University (lab head)
Robinson framed the result as transformative for his group’s work, noting that the combination of viral sequencing and single‑cell analysis enabled insights not previously possible. He and colleagues suggested the mechanism could account for the majority of SLE cases but acknowledged follow‑up work is essential to test that broad claim.
“They’ve done a lot and developed an interesting concept.”
Guy Gorochov, Virologist, Sorbonne University (external expert)
Sorbonne virologist Guy Gorochov described the study as technically impressive and conceptually provocative, while cautioning that it is not yet the definitive word on lupus causation. Independent validation across cohorts and further mechanistic work were highlighted as next steps by external commentators.
Unconfirmed
- The authors propose the mechanism may apply to 100% of lupus cases, but that universality has not been independently replicated across global cohorts.
- Whether specific EBV strains or host genetic differences explain why only some infected individuals develop SLE remains speculative and unproven.
- Direct causal proof in humans — showing EBV infection precedes and initiates lupus in prospective studies — is not yet available.
Bottom line
The Stanford study provides strong mechanistic evidence that EBV can infect and reprogram memory B cells in ways that plausibly drive systemic autoimmunity, and it substantially strengthens the argument that a common virus contributes to lupus pathogenesis. The technical advance in detecting rare, infected B cells is an important methodological milestone that removes a key obstacle to testing viral hypotheses in autoimmune disease.
However, caution is warranted: claims that EBV explains all lupus cases require replication in larger, diverse cohorts and longitudinal data to establish causality. If validated, the findings would redirect parts of lupus research and prevention toward antiviral strategies, vaccines and refined B‑cell interventions, with possible implications for other EBV‑associated disorders.
Sources
- ScienceAlert — news summary of the study (media)
- Science Translational Medicine — original peer‑reviewed journal (Sci. Transl. Med., 2025) (peer‑reviewed journal)
- Stanford University — institutional/academic source and laboratory affiliation (academic institution)