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1.
J Med Virol ; 96(4): e29595, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38587217

ABSTRACT

Systemic autoimmune diseases (SADs) are a growing spectrum of autoimmune disorders that commonly affect multiple organs. The role of Epstein-Barr virus (EBV) infection or reactivation as a trigger for the initiation and progression of SADs has been established, while the relationship between EBV envelope glycoproteins and SADs remains unclear. Here, we assessed the levels of IgG, IgA, and IgM against EBV glycoproteins (including gp350, gp42, gHgL, and gB) in serum samples obtained from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and found that RA and SLE patients exhibited a statistically significant increase in the levels of 8 and 11 glycoprotein antibodies, respectively, compared to healthy controls (p < 0.05). The LASSO model identified four factors as significant diagnostic markers for RA: gp350 IgG, gp350 IgA, gHgL IgM, and gp42 IgA; whereas for SLE it included gp350 IgG, gp350 IgA, gHgL IgA, and gp42 IgM. Combining these selected biomarkers yielded an area under the curve (AUC) of 0.749 for RA and 0.843 for SLE. We subsequently quantified the levels of autoantibodies associated with SADs in mouse sera following immunization with gp350. Remarkably, none of the tested autoantibody levels exhibited statistically significant alterations. Elevation of glycoprotein antibody concentration suggests that Epstein-Barr virus reactivation and replication occurred in SADs patients, potentially serving as a promising biomarker for diagnosing SADs. Moreover, the absence of cross-reactivity between gp350 antibodies and SADs-associated autoantigens indicates the safety profile of a vaccine based on gp350 antigen.


Subject(s)
Arthritis, Rheumatoid , Autoimmune Diseases , Epstein-Barr Virus Infections , Lupus Erythematosus, Systemic , Humans , Animals , Mice , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human , Antibodies, Viral , Arthritis, Rheumatoid/complications , Glycoproteins , Autoimmune Diseases/complications , Immunoglobulin G , Immunoglobulin A , Immunoglobulin M
2.
J Med Virol ; 95(5): e28793, 2023 05.
Article in English | MEDLINE | ID: mdl-37212266

ABSTRACT

Epstein-Barr virus (EBV) infection is prevalent in global population and associated with multiple malignancies and autoimmune diseases. During the infection, EBV-harbored or infected cell-expressing antigen could elicit a variety of antibodies with significant role in viral host response and pathogenesis. These antibodies have been extensively evaluated and found to be valuable in predicting disease diagnosis and prognosis, exploring disease mechanisms, and developing antiviral agents. In this review, we discuss the versatile roles of EBV antibodies as important biomarkers for EBV-related diseases, potential driving factors of autoimmunity, and promising therapeutic agents for viral infection and pathogenesis.


Subject(s)
Autoimmune Diseases , Epstein-Barr Virus Infections , Multiple Sclerosis , Humans , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/drug therapy , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human , Antibodies, Viral , Autoimmune Diseases/complications , Antiviral Agents/therapeutic use
3.
Signal Transduct Target Ther ; 7(1): 202, 2022 06 28.
Article in English | MEDLINE | ID: mdl-35764603

ABSTRACT

The persistent COVID-19 pandemic since 2020 has brought an enormous public health burden to the global society and is accompanied by various evolution of the virus genome. The consistently emerging SARS-CoV-2 variants harboring critical mutations impact the molecular characteristics of viral proteins and display heterogeneous behaviors in immune evasion, transmissibility, and the clinical manifestation during infection, which differ each strain and endow them with distinguished features during populational spread. Several SARS-CoV-2 variants, identified as Variants of Concern (VOC) by the World Health Organization, challenged global efforts on COVID-19 control due to the rapid worldwide spread and enhanced immune evasion from current antibodies and vaccines. Moreover, the recent Omicron variant even exacerbated the global anxiety in the continuous pandemic. Its significant evasion from current medical treatment and disease control even highlights the necessity of combinatory investigation of the mutational pattern and influence of the mutations on viral dynamics against populational immunity, which would greatly facilitate drug and vaccine development and benefit the global public health policymaking. Hence in this review, we summarized the molecular characteristics, immune evasion, and impacts of the SARS-CoV-2 variants and focused on the parallel comparison of different variants in mutational profile, transmissibility and tropism alteration, treatment effectiveness, and clinical manifestations, in order to provide a comprehensive landscape for SARS-CoV-2 variant research.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/genetics , Humans , Immune Evasion/genetics , Pandemics , SARS-CoV-2/genetics
4.
Nat Commun ; 12(1): 6624, 2021 11 16.
Article in English | MEDLINE | ID: mdl-34785638

ABSTRACT

Epstein-Barr virus (EBV) is associated with a range of epithelial and B cell malignancies as well as autoimmune disorders, for which there are still no specific treatments or effective vaccines. Here, we isolate EBV gH/gL-specific antibodies from an EBV-infected individual. One antibody, 1D8, efficiently neutralizes EBV infection of two major target cell types, B cells and epithelial cells. In humanized mice, 1D8 provides protection against a high-dose EBV challenge by substantially reducing viral loads and associated tumor burden. Crystal structure analysis reveals that 1D8 binds to a key vulnerable interface between the D-I/D-II domains of the viral gH/gL protein, especially the D-II of the gH, thereby interfering with the gH/gL-mediated membrane fusion and binding to target cells. Overall, we identify a potent and protective neutralizing antibody capable of reducing the EBV load. The novel vulnerable site represents an attractive target that is potentially important for antibody and vaccine intervention against EBV infection.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Epstein-Barr Virus Infections/immunology , Herpesvirus 4, Human/immunology , Animals , Antibodies, Neutralizing/chemistry , B-Lymphocytes/immunology , Crystallography, X-Ray , Epithelial Cells/immunology , Epitopes , Epstein-Barr Virus Infections/virology , Glycoproteins/chemistry , Humans , Membrane Fusion , Mice , Nerve Tissue Proteins/chemistry , Viral Proteins/metabolism , Virus Replication
5.
Infect Dis Poverty ; 8(1): 20, 2019 Mar 25.
Article in English | MEDLINE | ID: mdl-30905322

ABSTRACT

BACKGROUND: Helminths are endemic in more than half of the world's countries, raising serious public health concerns. Accurate diagnosis of helminth infection is crucial to control strategies. Traditional parasitological methods, serological tests and PCR-based assays are the major means of the diagnosis of helminth infection, but they are time-consuming and/or expensive, and sometimes provide inaccurate results. Loop mediated isothermal amplification (LAMP) assay, a sensitive, simple and rapid method was therefore developed for detection of helminths. This study aims to discuss the current status of application of LAMP on helminths detection and to make a comprehensive evaluation about this updated technology and its future outlook by comparing with several other diagnostic methods. MAIN BODY: This review summarizes LAMP assay applied for helminth detection and helminthiasis surveillance. The basic principle of LAMP is introduced to help better understand its characteristics and each reported assay is assessed mainly based on its detection sensitivity, specificity and limitations, in comparison with other common diagnostic tests. Moreover, we discuss the limitations of the assays so as to clarify some potential ways of improvement. CONCLUSIONS: Here, we summarize and discuss the advantages, disadvantages and promising future of LAMP in heliminth detection, which is expected to help update current knowledge and future perspectives of LAMP in highly sensitive and specific diagnosis and surveillance of helminthiasis and other parasitic diseases, and can contribute to the elimination of the diseases from endemic areas.


Subject(s)
Helminthiasis/diagnosis , Helminths/isolation & purification , Nucleic Acid Amplification Techniques/methods , Animals , DNA, Helminth , Food Microbiology , Humans , Polymerase Chain Reaction/methods , Sensitivity and Specificity
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