There is a potential link between the reactivation of latent Epstein-Barr virus (EBV) infection and the imbalance of immune regulation in systemic lupus erythematosus (SLE). We successfully constructed a mouse model of lupus-like changes induced by EBV recombinant multi-epitope peptides to study the molecular mechanism of SLE development caused by the reactivation of latent EBV infection.

Age-appropriate female C57/6J mice were subcutaneously injected for immunization. They were randomly divided into four groups (n=5 per group): PBS group, adjuvant group , 100 μg and 200 μg peptide groups. They were immunized three times at weeks 1, 3, and 5. After 8 weeks of treatment, they were randomly divided into 100 μg and PBS control groups (n=4 per group) and immunized at weeks 1, 3, 5, and 7. The observation period was extended to 30 weeks for blood and tissue collection. The experiment was repeated with a second batch of animals (n=10 per group) to verify the stability of the 100 μg dose-induced model. The observations included body weight, skin lesions, spleen and kidney size, renal function (serum creatinine, urine protein), autoantibodies, immunoglobulins, complement C3, inflammatory cytokines, and histopathology. Transmission electron microscopy was also used to examine the changes.

Compared with 8 weeks, after 30 weeks of subcutaneous injection immunization with peptides, the experimental group mice showed skin lesions, significant increases in serum creatinine and urine protein, abnormal autoantibodies, elevated immunoglobulins, complement C3, and cytokines. The results were statistically different from the control group. However, there were no significant changes in the proportion of peripheral blood immune cell subsets. At the same time, histopathological changes were observed, including chronic inflammation in the spleen with lymphoid tissue hyperplasia, local old hemorrhage, increased glomerular volume, mesangial cell proliferation, degeneration and swelling of renal tubular epithelial cells, interstitial inflammation in the kidney, and immune complex deposition in the glomeruli. Transmission electron microscopy revealed characteristic manifestations such as electron-dense deposits in the mesangial and tubular areas.

Our study constructed EBV latency-specific multi-epitope peptides and further used them to immunize mice, successfully inducing lupus-like changes. This innovative animal model is of great significance for revealing the key role of EBV latent infection reactivation in SLE. It also provides crucial support for targeted EBV intervention, evaluating drug efficacy in the model, and ultimately screening out more precise SLE treatment regimens for this population.