Introduction: Endometriosis (EMS) is characterized as a prevalent gynecological inflammatory disorder marked by the existence of endometrial tissues situated beyond the uterus. This condition leads to persistent pelvic pain and may contribute to infertility. In this investigation, we explored the potential mechanism underlying the development of endometriosis (EMS) triggered by transient exposure to either latent membrane protein 1 (LMP1) or Epstein-Barr virus (EBV) in a mouse model. Additionally, we examined the potential inhibitory effect of evodiamine (EDM) on EMS. Methods: Immortalized human endometrial stromal cells (HESC) or epithelial cells (HEEC) were transiently exposed to either EBV or LMP1. The presence of evodiamine (EDM) was assessed for its impact on estrogen receptor β (ERβ) expression, as well as on cell metabolism parameters such as redox balance, mitochondrial function, inflammation, and proliferation. Additionally, a mixture of LMP1-treated HESC and HEEC was administered intraperitoneally to generate an EMS mouse model. Different dosages of EDM were employed for treatment to evaluate its potential suppressive effect on EMS development. Results: Transient exposure to either EBV or LMP1 triggers persistent ERβ expression through epigenetic modifications, subsequently modulating related cell metabolism for EMS development. Furthermore, 4.0 µM of EDM can efficiently reverse this effect in in vitro cell culture studies. Additionally, 20 mg/kg body weight of EDM treatment can partly suppress EMS development in the in vivo EMS mouse model. Conclusion: Transient EBV/LMP1 exposure triggers permanent ERβ expression, favoring later EMS development, EDM inhibits EMS development through ERβ suppression. This presents a novel mechanism for the development of endometriosis (EMS) in adulthood stemming from early Epstein-Barr virus (EBV) exposure during childhood. Moreover, evodiamine (EDM) stands out as a prospective candidate for treating EMS.

BACKGROUND: Fatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent viruses and their impact on systemic immune function have been increasingly reported in other conditions where fatigue is a predominant symptom. Epstein-Barr virus (EBV) in particular has been associated with fatigue, including in long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome, but has not yet been explored within the context of stroke.
OBJECTIVE: We performed an exploratory analysis to determine if there is evidence of a relationship between EBV reactivation and post-stroke fatigue.
METHODS: In a chronic ischemic stroke cohort (> 5 months post-stroke), we assayed circulating EBV by qPCR and measured the titres of anti-EBV antibodies by ELISA in patients with high fatigue (FACIT-F < 40) and low fatigue (FACIT-F > 41). Statistical analysis between two-groups were performed by t-test when normally distributed according to the Shapiro-Wilk test, by Mann-Whitney test when the data was not normally distributed, and by Fisher\'s exact test for categorical data.
RESULTS: We observed a similar incidence of viral reactivation between people with low versus high levels of post-stroke fatigue (5 of 22 participants (24%) versus 6 of 22 participants (27%)). Although the amount of circulating EBV was similar, we observed an altered circulating anti-EBV antibody profile in participants with high fatigue, with reduced IgM against the Viral Capsid Antigen (2.244 ± 0.926 vs. 3.334 ± 2.68; P = 0.031). Total IgM levels were not different between groups indicating this effect was specific to anti-EBV antibodies (3.23 × 105 ± 4.44 × 104 high fatigue versus 4.60 × 105 ± 9.28 × 104 low fatigue; P = 0.288).
CONCLUSIONS: These data indicate that EBV is not more prone to reactivation during chronic stroke recovery in those with post-stroke fatigue. However, the dysregulated antibody response to EBV may be suggestive of viral reactivation at an earlier stage after stroke.

Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis, persistently infects over 90% of the human adult population and is associated with several human cancers. To establish life-long infection, EBV tampers with the induction of type I interferon (IFN I)-dependent antiviral immunity in the host. How various EBV genes help orchestrate this crucial strategy is incompletely defined. Here, we reveal a mechanism by which the EBV nuclear antigen 3A (EBNA3A) may inhibit IFNβ induction. Using proximity biotinylation we identify the histone acetyltransferase P300, a member of the IFNβ transcriptional complex, as a binding partner of EBNA3A. We further show that EBNA3A also interacts with the activated IFN-inducing transcription factor IRF3 that collaborates with P300 in the nucleus. Both events are mediated by the N-terminal domain of EBNA3A. We propose that EBNA3A limits binding of IRF3 to the IFNβ promoter, thereby hampering downstream IFN I signaling. Collectively, our findings suggest a new mechanism of immune evasion by EBV, affected by its latency gene EBNA3A.

Etoposide has revolutionized the treatment of primary as well as secondary hemophagocytic lymphohistiocytosis (HLH), and it is, together with corticosteroids, the most widely used therapy for HLH. In the early 1980s, long-term survival in primary HLH was <5% but with the etoposide-/dexamethasone-based protocols HLH-94 and HLH-2004, in combination with stem cell transplantation, 5-year survival increased dramatically to around 60% in primary HLH, and based on analyses from the HLH-2004 study, there is likely room for further improvement. Biologically, etoposide administration results in potent selective deletion of activated T cells as well as efficient suppression of inflammatory cytokine production. Moreover, etoposide has also been reported to promote programmed cell death (apoptosis) rather than proinflammatory lytic cell death (pyroptosis), conceivably ameliorating subsequent systemic inflammation, i.e., a treatment very suitable for cytokine storm syndromes (CSS). The combination of etoposide and corticosteroids may also be beneficial in cases of severe or refractory secondary HLH (sHLH) with imminent organ failure, such as infection-associated HLH caused by Epstein-Barr virus (EBV) or malignancy-triggered HLH. In CSS associated with rheumatic diseases (macrophage activation syndrome, MAS or MAS-HLH), etoposide is currently used as second- or third-line therapy. Recent studies suggest that etoposide perhaps should be part of an aggressive therapeutic intervention for patients with severe refractory or relapsing MAS, in particular if there is CNS involvement. Importantly, awareness of sHLH must be further increased since treatment of sHLH is often delayed, thereby missing the window of opportunity for a timely, effective, and potentially life-saving HLH-directed treatment.

Hemophagocytic lymphohistiocytosis (HLH) has been described for decades in association with malignancies (M-HLH). While its mechanism is unknown, M-HLH has a poor prognosis, ranging from 10% to 30% overall survival. Mature T-cell lymphomas, diffuse large B-cell lymphoma, and Hodgkin lymphoma, with or without viral co-triggers such as Epstein-Barr virus, are among the most frequent underlying entities. Most M-HLH cases occur at the presentation of malignancy, but they may also occur during therapy as a result of immune compromise from chemotherapy (HLH in the context of immune compromise, IC-HLH) and (typically) disordered response to infection or after immune-activating therapies (Rx-HLH, also known as cytokine release syndrome, CRS). IC-HLH typically occurs months after diagnosis in the context of fungal, bacterial, or viral infection, though it may occur without an apparent trigger. Rx-HLH can be associated with checkpoint blockade, chimeric antigen receptor T-cell therapy, or bispecific T-cell engaging therapy. Until recently, M-HLH diagnosis and treatment strategies were extrapolated from familial HLH (F-HLH), though optimized diagnostic and therapeutic treatment strategies are emerging.

BACKGROUND: Epstein-Barr virus (EBV) can be reactivated and proliferated with fatal outcome in immuno-compromised people, but the clinical consequences of EBV infection in patients with severe fever with thrombocytopenia syndrome (SFTS) remain uncertain. In this study, we investigated the infection rate, the influence and the early predictors of EBV infection in SFTS patients.
METHODS: In this retrospective study, SFTS patients who were treated in the First Affiliated Hospital of Nanjing Medical University from May 2011 to August 2021 were enrolled and divided into infected and non-infected groups. We compared the demographic characteristics, clinical manifestations and signs, laboratory tests and prognosis, and explored the risk factors of EBV infection by receiver operating characteristic (ROC) curve and logistic regression.
RESULTS: A total of 120 hospitalized SFTS patients with EBV-DNA testing were enrolled in this study. Patients with EBV infection had statistically significant higher mortality rate (32.0% vs. 11.43%, P = 0.005). Compared with the non-infected group, the EBV-infected group had higher levels of C-reactive protein (CRP), creatine-kinase (CK), fasting blood glucose (FBG), blood urea nitrogen (BUN), D-dimer, and CD56+ cell counts, lower levels of immunoglobulin G (IgG), IgM, complement 3 (C3), and C4. The proportion of patients with age ≥ 60 years and ferritin > 1500.0 ng/ml in the EBV-infected group was significantly higher than that in the non-infected group. The results of ROC analysis showed that the cut-off values of CRP, IgG, C3, C4, and CD56+ cell counts to predict EBV infection were 13.2 mg/l, 12.5 g/l, 1.1 g/l, 0.6 g/l, 0.3 g/l, and 94.0 cells/µl. Multivariable logistic analysis showed that age ≥ 60 years old, CRP > 13.2 mg/l, BUN > 5.4 mmol/l, ferritin > 1500.0 ng/ml, IgG < 12.5 g/l, IgM < 1.1 g/l, C4 < 0.3 g/l, and CD56+ cell counts > 94.0 cells/µl were the independent risk factors of EBV infection in SFTS patients.
CONCLUSIONS: SFTS combined with EBV infection is associated with high morbidity and mortality. It is necessary to strengthen screening for EBV infection and its early predictive markers after admission in SFTS patients.

Epstein-Barr virus (EBV) infection has a strong correlation with the development of nasopharyngeal carcinoma (NPC). Aquaporin 3 (AQP3), a member of the aquaporin family, plays an important role in tumor development, especially in epithelial-mesenchymal transition. In this study, the expression of AQP3 in EBV-positive NPC cells was significantly lower than that in EBV-negative NPC cells. Western blot and qRT-PCR analysis showed that LMP1 down-regulated the expression of AQP3 by activating the ERK pathway. Cell biology experiments have confirmed that AQP3 affects the development of tumor by promoting cell migration and proliferation in NPC cells. In addition, AQP3 can promote the lysis of EBV in EBV-positive NPC cells. The inhibition of AQP3 expression by EBV through LMP1 may be one of the mechanisms by which EBV maintains latent infection-induced tumor progression.

Epstein-Barr virus (EBV) is deemed a necessary, yet insufficient factor in the development of multiple sclerosis (MS). In this study, myelin basic protein-specific transgenic T cell receptor mice were infected with murid gammaherpesvirus 68 virus (MHV68), an EBV-like virus that infects mice, resulting in the onset neurological deficits at a significantly higher frequency than influenza or mock-infected mice. MHV68 infected mice exhibited signs including optic neuritis and ataxia which are frequently observed in MS patients but not in experimental autoimmune encephalomyelitis mice. MHV68-infected mice exhibited increased focal immune cell infiltration in the central nervous system. Single cell RNA sequencing identified the emergence of a population of B cells that express genes associated with antigen presentation and costimulation, indicating that gammaherpesvirus infection drives a distinct, pro-inflammatory transcriptional program in B cells that may promote autoreactive T cell responses in MS.

Epstein-Barr virus (EBV) is the first human oncogenic virus known to express microRNAs (miRNAs), which are closely associated with the development of various tumors, including nasopharyngeal and gastric cancers. Stearoyl-CoA Desaturase 1 (SCD1) is a key enzyme in fatty acid synthesis, highly expressed in numerous tumors, promoting tumor growth and metastasis, making it a potential therapeutic target. In this study, we found that SCD1 expression in EBV-associated gastric cancer (EBVaGC) was significantly lower than in EBV-negative gastric cancer (EBVnGC) at both cellular and tissue levels. In addition, EBV-miR-BART20-5p targets the 3\'-UTR of SCD1, downregulating its expression. Moreover, overexpression of SCD1 in EBVaGC cells promoted cell migration and proliferation while inhibiting autophagy. These results suggest that EBV-encoded miRNA-BART20-5p may contribute to EBVaGC progression by targeting SCD1.

Epstein-Barr virus (EBV) is a ubiquitous and potentially oncogenic human herpesvirus. In this article, we discuss a rare case of primary testicular NK/T-cell lymphoma, nasal type, associated with high plasma Epstein-Barr virus DNA load. The patient, a 45-year-old man, presented with painful testicular swelling, fever, and weight loss. An orchiectomy revealed tumor proliferation, which was diagnosed as testicular NK/T cell lymphoma, nasal type, confirmed by immunohistochemistry, and classified as stage IV according to the Ann Arbor classification. The patient was treated with SMILE chemotherapy. After treatment, a PET scan showed complete remission with negative EBV DNA levels. The discussion focused on the role of EBV in the development of this malignant lymphoproliferation and the importance of quantifying EBV DNA load by real-time PCR in assessing prognosis, patient follow-up, and response to treatment.