Aberrant Epstein-Barr viral infection in systemic lupus erythematosus

Abstract

Serologic association, cross-reactivity of select EBV-specific antibodies with SLE autoantigens, SLE-like autoimmunity after immunization with EBV peptides, increased EB viral load in SLE patients, and SLE-specific alterations in EBV humoral and cellular immunity implicate Epstein-Barr virus (EBV) in the development of systemic lupus erythematosus (SLE). To investigate SLE-specific differences in EBV gene expression, levels of eight EBV genes were compared between SLE patients and controls by using both ex vivo-infected and un-manipulated peripheral blood mononuclear cells (PBMCs). Expression levels of mRNA were significantly greater by Wilcoxen signed rank test in the ex vivo-infected SLE patient-derived cells for 4 of 8 EBV genes, including BLLF1, 3.2-fold (p<0.004); LMP-2, 1.7-fold (p<0.008); EBNA-1, 1.7-fold (p<0.01); and BcRF1, a proposed DNA binding protein, 1.7-fold (p<0.02). The frequency of LMP-1 gene expression was significantly greater by Chi square analysis in the peripheral blood from SLE patients than controls (44% of patients, 10% of controls p<0.05). PBMCs from SLE patients had greater expression of latent genes as well as increased expression of both latent and lytic genes after infection, suggesting that EBV may participate in SLE etiology through several mechanisms. Such altered infection patterns may contribute to the increased levels of EBV and the molecular mimicry seen in sera from SLE patients.

Fig.1

EBV gene expression in SLE patients and controls. EBV gene expression was analyzed by real-time PCR.A. Significant increases in expression of 4 genes were found in 12-day cultures of EBV-infected cells from SLE patients compared to EBV-infected cells from controls (n=10 pairs). Gene expression is shown in terms of mean fold increase in the patient samples compared to controls. Error bars indicate standard error. B. Both lytic (BLLF1 and BCRF1) and latent (EBER 1, EBNA-1, LMP-1, and LMP-2) gene expression was detected in PBMCs from both patients and controls immediately after isolation. LMP-1 expression was significantly greater in freshly isolated PBMCs from patients than from controls (p<0.05, n=6 patients, 9 controls).