Search Results (950)

Porcine lymphotropic herpesviruses -1, -2, and -3 (PLHV-1, PLHV-2, and PLHV-3) are gammaherpesviruses that are widespread in pigs. These viruses are closely related to the human pathogens Epstein–Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), both of which are known to cause severe diseases in humans. To date, however, no definitive association has been established between PLHVs and any disease in pigs. With the growing interest in xenotransplantation as a means to address the shortage of human organs for transplantation, the safety of using pig-derived cells, tissues, and organs is under intense investigation. In preclinical trials involving pig-to-nonhuman primate xenotransplantation, another porcine herpesvirus—porcine cytomegalovirus, a porcine roseolovirus (PCMV/PRV)—was shown to be transmissible and significantly reduced the survival time of the xenotransplants. In the present study, we examined donor pigs and their respective baboon recipients, all of which were part of preclinical pig heart xenotransplantation studies, for the presence of PLHV. PLHV-1, PLHV-2, and PLHV-3 were detected in nearly all donor pigs; however, no evidence of PLHV transmission to the baboon recipients was observed. Full article

The Epstein–Barr virus (EBV) is a prevalent virus linked to various diseases, including infectious mononucleosis (IM), nasopharyngeal carcinoma, and Hodgkin’s lymphoma. Over the past few decades, EBV diagnostic strategies have evolved significantly—progressing from traditional serological assays and histopathology to more sensitive and specific molecular techniques such as nucleic acid amplification and high-throughput sequencing (HTS). While conventional methods remain valuable for their accessibility and established clinical use, they are often limited by sensitivity, speed, and multiplexing capability. In contrast, emerging technologies, including isothermal amplification, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based diagnostics, multi-omics integration, and AI-assisted analysis, have demonstrated great promise in improving diagnostic accuracy, speed, and applicability in diverse clinical settings, including point-of-care testing (POCT). This review systematically explores the historical development of EBV diagnostic technologies, highlighting key milestones and future trends in precision medicine and global health readiness. Full article

Background/Objectives: Since the World Health Organization (WHO) recommended HIV self-testing as an alternative to traditional facility-based testing in 2016, it has been increasingly adopted worldwide. This study aimed to evaluate the performance of the ConfiSign HIV Self-Test (GenBody Inc., Republic of Korea), a newly developed blood-based immunochromatographic assay for the qualitative detection of total antibodies (IgG and IgM) against HIV-1/HIV-2. Methods: The evaluation included four components: (1) retrospective analysis of 1400 archived serum samples (400 HIV-positive and 1000 HIV-negative samples), (2) prospective self-testing by 335 participants (112 HIV-positive participants and 223 individuals with an unknown HIV status, including healthy volunteers), (3) assessment using seroconversion panels and diverse HIV subtypes, and (4) analytical specificity testing for cross-reactivity and interference. The Elecsys HIV combi PT and Alinity I HIV Ag/Ab Combo assays were used as reference assays. Results: In retrospective testing, the ConfiSign HIV Self-Test achieved a positive percent agreement (PPA) of 100%, a negative percent agreement (NPA) of 99.2%, and a Cohen’s kappa value of 0.986, showing excellent agreement with the reference assays. In the prospective study, the test showed 100% sensitivity and specificity, with a low invalid result rate of 1.8%. All HIV-positive samples, including those with low signal-to-cutoff (S/Co) values in the Alinity I assay, were correctly identified. The test also reliably detected early seroconversion samples and accurately identified a broad range of HIV-1 subtypes (A, B, C, D, F, G, CRF01_AE, CRF02_AG, and group O) as well as HIV-2. No cross-reactivity or interference was observed with samples that were positive for hepatitis viruses, cytomegalovirus, Epstein–Barr virus, varicella zoster virus, influenza, HTLV-1, HTLV-2, or malaria. Conclusions: The ConfiSign HIV Self-Test demonstrated excellent sensitivity, specificity, and robustness across diverse clinical samples, supporting its reliability and practicality as a self-testing option for HIV-1/2 antibody detection. Full article

Epidemiological studies identified insufficient and poor-quality sleep as independent risk factors for multiple sclerosis (MS). The glymphatic system, active during slow-wave sleep, clears brain waste through perivascular astrocytic aquaporin-4 (AQP4) channels. The presence of antigens induces a transient, physiological lowering of glymphatic flux as a first step of an inflammatory response. A possible hypothesis linking infection with the Epstein–Barr virus, a well identified causal step in MS, and the development of the disease is that mechanisms such as poor sleep or less functional AQP4 polymorphisms may sustain glymphatic flow reduction. Such chronic glymphatic reduction would trigger a vicious circle in which the persistence of antigens and an inflammatory response maintains glymphatic dysfunction. In addition, viral proteins that persist in demyelinated plaques can depolarize AQP4, further restricting waste elimination and sustaining local inflammation. This review examines the epidemiological evidence connecting sleep and MS risk, and the mechanistic findings showing how poor sleep and other glymphatic modulators heighten inflammatory signaling implicated in MS pathogenesis. Deepening knowledge of glymphatic functioning in MS could open new avenues for personalized prevention and therapy. Full article

Herpesviruses are DNA viruses that evade the immune response and persist as lifelong infections. Human gamma-herpesviruses Epstein–Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV) are oncogenic; they can lead to cancer. Oncogenic viruses are responsible for 10–15% of human cancer development, which can have poor prognoses. Non-coding RNAs (ncRNAs) are RNAs that regulate gene expression without encoding proteins, and are being studied for their roles in viral immune evasion, infection, and oncogenesis. ncRNAs are classified by their size, and include long non-coding RNAs, microRNAs, and circular RNAs. EBV and KSHV manipulate host ncRNAs, and encode their own ncRNAs, regulating host processes and immune responses. Viral ncRNAs regulate host functions by post-transcriptionally modifying host RNAs, and by serving as mimics of other host RNAs, promoting immune evasion. ncRNAs in gamma-herpesvirus infection are also important for tumorigenesis, as dampening immune responses via ncRNAs can upregulate pro-tumorigenic pathways. Emerging topics such as RNA modifications, target-directed miRNA degradation, competing endogenous RNA networks, and lncRNA/circRNA–miRNA interactions provide new insights into ncRNA functions. This review compares ncRNAs and the mechanisms of viral immune evasion in EBV and KSHV, while also expanding on recent developments in the roles of ncRNAs in immune evasion, viral infection, and oncogenesis. Full article

Objectives: Our objective was to investigate the clinical characteristics, complications, and treatment outcomes of Epstein–Barr virus (EBV)-related infectious mononucleosis (IM) in children and to identify risk factors associated with prolonged fever and abnormal liver function. Methods: This retrospective study included 3006 children admitted to Shenzhen Children’s Hospital from May 2009 to April 2024 with suspected EBV-related IM. After excluding cases without etiological evidence and those with underlying diseases, 2660 cases were analyzed. Data on demographics, clinical manifestations, laboratory findings, complications, and treatment outcomes were collected. Logistic regression was used to identify risk factors for prolonged fever and abnormal liver function. Results: Among the 2660 confirmed cases, patients ranged from 8 months to 17 years of age, with a median age of 4 years and a male-to-female ratio of 1.46:1. Co-infections were identified in 369 (13.9%) patients, predominantly with Group A Streptococcus. Complications occurred in 560 (24.46%) of the 2289 patients without co-infections, with bronchitis being the most common (42.68%). Elevated ferritin and atypical lymphocyte percentage were associated with prolonged fever (p < 0.001), while elevated lactate dehydrogenase (LDH) and a lower CD4% predicted abnormal liver function (p < 0.001). Antiviral therapy did not shorten fever duration or hospital stay but prolonged both when combined with corticosteroids or intravenous immunoglobulin (IVIG) (p < 0.001). Conclusions: Specific laboratory markers such as ferritin, atypical lymphocyte percentage, LDH, and CD4% are important predictors of prolonged fever or liver dysfunction in EBV-IM. Our findings suggest that antiviral therapy may not be beneficial in uncomplicated cases and highlight the need for tailored treatment strategies to optimize patient outcomes. Full article

Oncoviruses, such as Epstein–Barr virus (EBV), human papillomavirus (HPV), and Kaposi sarcoma-associated herpesvirus (KSHV), have been widely discussed for their oncogenic risk. Initially, the oral cavity was disregarded. In recent years, orientation has shifted to the importance of the oral cavity and cancer-related issues via Handbook 19 titled “Oral Cancer Prevention” by the International Agency for Research on Cancer, the WHO Global Oral Health Status Report 2022, and multiple other actions focused on reducing the oversight of this neglected area. Oncoviruses play a significant role in oral cavity malignancies by establishing persistent infections, evading host immune responses, and inducing cellular transformation through the disruption of normal regulatory pathways. Molecular biology and microbiome research have advanced our understanding of the complex interplay between oncoviruses and oral microbiota, demonstrating how coinfections and dysbiosis can enhance viral oncogenic potential. These findings improve the understanding of virus-induced oral cancers and support the development of novel diagnostic and therapeutic strategies. This narrative review focuses on the relationship between oncoviruses and the oral cavity by focusing on how a specific virus triggers tumorigenesis for each of the described viruses and how it affects oral cavity cancer development. Finally, we describe recent advances and future perspectives including vaccines and/or treatment. Full article

Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition that can go underdiagnosed due to overlapping features with severe infections. While the use of thiopurine in inflammatory bowel disease (IBD) has been associated with HLH, the majority of these patients will have a concurrent Epstein–Barr virus (EBV) infection. Case Presentation: This report presents a case of HLH in a patient previously treated with aza-thioprine for IBD without concurrent viral infection. Full article

The Epstein–Barr virus (EBV) is the first human herpesvirus identified as an oncogenic agent, with approximately 95% of adults worldwide being latently infected. EBV infection is associated with multiple diseases, including nasopharyngeal carcinoma, Hodgkin’s lymphoma, infectious mononucleosis, and multiple sclerosis. Given significant EBV-associated disease burden, developing effective vaccines against EBV remains a priority. In this review, we first presented the current understanding of EBV biology and pathogenesis, focusing on its biological structure and immune evasion mechanisms, and discussed key viral antigens—including gp350, gp42, gH/gL, and latency proteins—as potential targets for EBV vaccine development. We also summarized recent advances in various EBV vaccine platforms, including subunit, viral vector-based, nanoparticle-based, and mRNA vaccines, and discussed the related preclinical and clinical evidence, although no effective EBV vaccine has been approved for clinical use yet. In summary, this review provides an overview of the current landscape in EBV vaccine research, and sheds new light on developing new therapeutic approaches against EBV-associated diseases. Full article

Epstein–Barr virus (EBV) is the first oncogenic DNA virus known to encode microRNAs (miRNAs) and has been implicated in the pathogenesis of multiple malignancies, including a distinct subset of gastric cancers (EBV-associated gastric cancer, EBVaGC). However, the functional roles of individual EBV-encoded miRNAs in EBVaGC remain poorly defined. In this study, we integrate bioinformatic and experimental analyses to uncover a novel oncogenic axis driven by EBV-encoded miR-BART20-3p. Analysis of public transcriptomic datasets revealed that peroxisome proliferator-activated receptor α (PPARα) is significantly downregulated in EBVaGC compared with EBV-negative gastric tumors. We confirmed that both PPARα mRNA and protein are reduced in EBVaGC cell lines and primary tumor specimens, and that this reduction inversely correlates with miR-BART20-3p levels. A dual-luciferase reporter assay demonstrated that miR-BART20-3p directly binds the PPARα 3′-UTR. Functionally, miR-BART20-3p overexpression in AGS cells enhanced proliferation and migration, whereas inhibition of miR-BART20-3p in EBV-infected AGS cells attenuated these phenotypes. Mechanistic studies employing PPARα-specific siRNA together with qRT-PCR and ELISA reveal that suppression of PPARα or overexpression of miR-BART20-3p leads to upregulation of interleukin 6 (IL-6), indicating disruption of the PPARα–IL-6 regulatory axis. Collectively, EBV-encoded miR-BART20-3p promotes EBVaGC progression by directly targeting PPARα, and thereby derepressing IL-6 expression. This miRNA–PPARα–IL-6 pathway may serve as both a mechanistic biomarker and a novel therapeutic target in EBVaGC. Full article

Background/Objectives: Breast cancer (BC) is the most common source of new cancer diagnoses among women and the second leading cause of cancer-related deaths in this group. The role of viral factors in the etiology, heterogeneity, and pathogenesis of this disease and its subtypes has not been incontrovertibly determined. Thus, in this study we began to address this problem by testing the hypothesis that the oncogenic Epstein–Barr virus (EBV) plays a role in this process. The approach involved determining the differential expression and predicted role of EBV gene sequences present in various subtypes of breast tumors as compared to those in control normal tissues. Methods: We utilized existing deep sequencing RNA-seq datasets derived from seventeen breast tumors and three control normal breast tissue samples to investigate the differential expression of EBV gene sequences. Results: We report three-fold higher levels of normalized total EBV-expressed sequences in tumors as compared to in control breast tissue. We also demonstrate differential expression of EBV gene transcript sequences in four categories of 26 known genes in breast cancer tumors as compared to that in normal breast tissue controls. Tumor-specific expression of EBV gene transcript sequences localized to seventeen genes; of these, tumor-specific EBV gene transcript-expressed sequences localizing to nine genes were strongly differentially expressed in a breast cancer subtype-specific manner. Furthermore, in a proof-of-concept investigation, we report, for the first time, that functional analysis of the differentially expressed integrated EBV transcript sequences demonstrate the capacity of these sequences to generate novel EBV miRNAs. We conclude that these integrated EBV sequences could potentially play a role in the pathogenesis of BC and its most aggressive subtypes. The functional role of these findings is currently under study. Full article

AIDS-related malignant lymphomas (ARLs) are the lymphomas that develop in association with HIV infection. According to the introduction of combination antiretroviral therapy (cART), the life expectancy of People Living with HIV (PLWH) has markedly improved; however, approximately one-third of PLWH have passed away from the complications of malignancies, even in well-controlled PLWH. HIV itself is not tumorigenic, and most of these tumors are due to co-infection with oncogenic viruses. γ-herpes viruses (Epstein–Barr virus: EBV and Kaposi sarcoma-associated herpesvirus: KSHV) are the most significant risk factors for ARLs. Immunodeficiency, chronic inflammation, accelerated aging, and genetic instability caused by HIV infection, as well as HIV accessory molecules, are thought to promote lymphomagenesis. The prognosis of ARLs is comparable to that of non-HIV cases in the cART era. Intensive chemotherapy with autologous stem cell transplantation is also available for relapsed/refractory ARLs. Since the early stage of HIV infection has no symptoms, significant numbers of HIV-infected individuals have not noticed HIV infection until the onset of AIDS (so-called Ikinari AIDS). Since the ratio of these patients is more than 30% in Japan, hematologists should carefully consider the possibility of HIV infection in cases of lymphoma. Even in an era of cART, ARL remains a critical complication in PLWH, warranting continuous surveillance. Full article

Despite the significant decrease in SARS-CoV-2-related mortality, COVID-19 continues to impose a high public health burden due to the high rate of post-COVID-19 pathological conditions, broadly termed Long COVID, that continue for any period of time and are generally multisystemic. However, recent studies have strengthened the evidence that the reactivation of the Epstein–Barr virus (EBV) in the post-COVID-19 era has significantly contributed to the exacerbation and prolongation of Long COVID symptoms. The mechanism and pathophysiology of EBV reactivation in Long COVID patients still need further exploration due to limited studies. This review summarises the various studies linking EBV reactivation in Long COVID along with its pathophysiology and novel therapeutics for EBV in a post-COVID-19 era. Full article

Epstein–Barr virus (EBV), a double-stranded DNA virus, is implicated in nasopharyngeal carcinoma (NPC), with particularly high incidence in regions such as southern China and Hong Kong. Although NPC is typically treated with radio- and chemotherapy, outcomes remain poor for advanced-stage diagnoses, highlighting the need for targeted therapies. This study explores the potential of CRISPR/CRISPR-associated protein 13 (Cas13) technology to target essential EBV RNA in NPC cells. Previous research demonstrated that CRISPR/Cas9 could partially reduce EBV load, but suppression was incomplete. Here, the combination of CRISPR/Cas13 with CRISPR/Cas9 shows enhanced viral clearance. Long-term EBNA1 suppression via CRISPR/Cas13 reduced the EBV genome, improved CRISPR/Cas9 effectiveness, and identified suitable AAV serotypes for delivery. Furthermore, cotreatment increased NPC cell sensitivity to 5-fluorouracil and cisplatin. These findings underscore the potential of CRISPR/Cas13 as an anti-EBV therapeutic approach, effectively targeting latent EBV transcripts and complementing existing treatments. The study suggests a promising new direction for developing anti-EBV strategies, potentially benefiting therapies for NPC and other EBV-associated malignancies. Full article

Background and Objectives: The Epstein-Barr virus (EBV) belongs to the gamma herpesviruses family. Evidence from the literature suggests that EBV initiates immune responses and the production of antibodies. Chronic or recurrent EBV infections may be associated with autoimmune diseases such as systemic lupus erythematosus, Sjögren’s syndrome, rheumatoid arthritis, multiple sclerosis, or inflammatory bowel diseases. This review aims to establish the role of EBV in the development and progression of autoimmune diseases. Materials and Methods: A literature search was conducted using PubMed, PMC, Google Scholar, and SCOPUS. Relevant studies, including meta-analyses, case-control studies, literature reviews, cross-sectional studies, and longitudinal studies, were identified through titles and abstracts screening for a comprehensive analysis. Results: Our study revealed a strong association between EBV infection and several autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. Epstein-Barr virus seropositivity was significantly higher in affected individuals. Elevated EBV-specific antibodies correlated with disease onset and severity. EBV DNA and latency proteins were detected in diseased tissues, alongside immune dysregulation and molecular mimicry mechanisms. Conclusions: Our findings highlight that EBV may be an important factor in autoimmune disease pathogenesis, contributing to immune activation and tissue damage. Further research is needed to explore EBV-targeted therapies and their potential in preventing or managing autoimmune diseases. Full article