Epstein–Barr virus infection and type I interferon signature in patients with systemic lupus erythematosus

Abstract

Epstein-Barr (EB) virus infection has long been speculated to evoke systemic lupus erythematosus (SLE). Since a virus infection can induce interferon (IFN) system activation, we aimed to discover the relationship between the two in the progression of SLE in a Chinese inpatient cohort. Methods Peripheral blood mononuclear cells and sera were isolated from 116 SLE patients and 76 healthy controls. Antibodies against EBV-VCA (IgM and IgG) and EBNA (IgG) along with IFNα in patient sera were detected with enzyme-linked immunosorbent assays. The EB virus DNA load was detected by real-time quantitative polymerase chain reaction. Peripheral blood mononuclear cells both from patients and controls were isolated immediately. The mRNA from these samples was subjected to real-time PCR for the latent genes EBNA1, EBNA2 and LMP1 of EB virus, as well as four IFN-stimulated genes (ISGs) ( OASL, MX1, ISG15 and LY6E). The antibody results were used to determine the stage of EBV infection (lytic, latent, or previous). Results SLE patients had a higher rate of lytic infection defined as positive EBV-VCA IgM antibody (39.66% vs 10.53%, p = 0.027), but not the EB virus DNA load. Patients with lytic EB virus infection had higher SLEDAI scores than patients with non-lytic infection (15.24 ± 2.63 vs 13.79 ± 3.24, p = 0.012). LMP1 was the only EBV gene that had a higher expression level in SLE patients than in healthy controls (3.26 ± 2.95 vs 1.00 ± 2.89, p = 0.000). It was also positively correlated with SLEDAI scores ( r = 0.462, p = 0.000). Levels of IFNα and the four ISGs were all significantly higher in SLE patients than in healthy controls ( p < 0.05). LMP1 was positively correlated with the four ISGs ( r = 0.403 ∼ 0.494, p < 0.05) in SLE patients but not in healthy controls ( r = -0.153 ∼ 0.129, p > 0.05). Neither EBNA1 nor EBNA2 was correlated with the ISGs in SLE patients or in healthy controls. Conclusions The SLE patients had higher rates of lytic EB virus infection and higher latent gene LMP1 expression, which might be associated with the development and/or the progression of SLE via the type I IFN pathway. The underlying mechanism needs more study.

Dysbiosis in Peripheral Blood Mononuclear Cell Virome Associated With Systemic Lupus Erythematosus

“…Compared to the results of previous studies, unexpectedly, we did not detect HFV, HHV6, and HTLV in PBMCs of SLE patients. We also did not detect HHV8 (Naganuma et al, 2008;Broccolo et al, 2013), but EBV (Han et al, 2018) and HHV5 (Chen et al, 2015) were detected in PBMCs of SLE patients, as in previous studies. In addition, the diagnostic capabilities of two viruses, namely HHV5 and HHV8 (screened by Random Forests-based backward feature selection; Figure 2A), which might serve as SLE markers, were selected and discussed in this study based on previously published data.…”

“…Previous research showed that many viruses are present in PBMCs. Human foamy virus (HFV) (Sun et al, 2006), Epstein-Barr virus (EBV) (Han et al, 2018), human T lymphotropic virus type I (HTLV) (Akimoto et al, 2007), human cytomegalovirus (HCMV) (Chen et al, 2015), and human herpesvirus 6 (HHV6) (Broccolo et al, 2013) exist in PBMCs or peripheral blood leukocytes of SLE patients. Although some viruses have been detected in PBMCs of SLE, virome diversity and variations in the PBMC microbial flora remain unexplored.…”

Sensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia

“…A collection of genes associated with inflammation, interferon I and II activity in addition to neutrophil and macrophage deregulators were also differentially expressed between EBV positive and negative samples. These genes include MX1, ANAX2P2, DEFA1, NCF1C, CLC, and SPIB 24–27 . GO biological enrichment analysis found enrichments including an increase in reactive oxygen species and metabolic cell processing pathways when the tumor samples were classified as EBV positive (ROS metabolic process).…”

Autophagy and immunological aberrations in systemic lupus erythematosus

“…Notably, it was observed that EB virus loads are significantly higher in patients with active SLE . The patients with SLE had higher rate of latent membrane protein 1 (LMP1) expression, which was positively correlated with the IFN‐stimulated genes . Latent membrane protein 1 (LMP1) of EBV was observed to induce autophagy.…”