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1.
Proc Natl Acad Sci U S A ; 119(32): e2202371119, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35917353

RESUMO

Epstein-Barr virus (EBV) infects more than 90% of the world's adult population and accounts for a significant cancer burden of epithelial and B cell origins. Glycoprotein B (gB) is the primary fusogen essential for EBV entry into host cells. Here, we isolated two EBV gB-specific neutralizing antibodies, 3A3 and 3A5; both effectively neutralized the dual-tropic EBV infection of B and epithelial cells. In humanized mice, both antibodies showed effective protection from EBV-induced lymphoproliferative disorders. Cryoelectron microscopy analyses identified that 3A3 and 3A5 bind to nonoverlapping sites on domains D-II and D-IV, respectively. Structure-based mutagenesis revealed that 3A3 and 3A5 inhibit membrane fusion through different mechanisms involving the interference with gB-cell interaction and gB activation. Importantly, the 3A3 and 3A5 epitopes are major targets of protective gB-specific neutralizing antibodies elicited by natural EBV infection in humans, providing potential targets for antiviral therapies and vaccines.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Proteínas Virais , Animais , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/química , Anticorpos Antivirais/isolamento & purificação , Anticorpos Antivirais/uso terapêutico , Microscopia Crioeletrônica , Infecções por Vírus Epstein-Barr/prevenção & controle , Infecções por Vírus Epstein-Barr/terapia , Herpesvirus Humano 4/imunologia , Humanos , Fusão de Membrana , Camundongos , Proteínas Virais/imunologia
3.
Front Immunol ; 13: 829943, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154153

RESUMO

Tumor cells of classic Hodgkin lymphoma (cHL) are derived from antigen presenting B cells that are infected by Epstein Barr virus (EBV) in ~30% of patients. Polymorphic Killer cell immunoglobulin-like receptors (KIRs) expressed on NK cells interact with human leukocyte antigen (HLA) class I and play a key role in immune surveillance against virally infected cells and tumor cells. We investigated the effect of KIR types on cHL susceptibility overall (n=211) and in EBV-stratified subgroups using the Dutch GoNL cohort as controls (n=498). The frequency of the KIR haplotype B subgroup was significantly different between EBV+ and EBV- cHL patients (62% vs. 77%, p=0.04) and this difference was more pronounced in nodular sclerosis (NS) cHL (49% vs. 79%, p=0.0003). The frequency of KIR haplotype B subgroup was significantly lower in EBV+ NS cHL compared to controls (49% vs. 67%, p=0.01). Analyses of known KIR - HLA interaction pairs revealed lower carrier frequencies of KIR2DS2 - HLA-C1 (29% vs. 46%, p=0.03) and KIR2DL2 - HLA-C1 (29% vs. 45%, p=0.04) in EBV+ NS cHL patients compared to controls. Carriers of the KIR haplotype B subgroup are less likely to develop EBV+ NS cHL, probably because of a more efficient control over EBV-infected B cells.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/imunologia , Doença de Hodgkin/imunologia , Receptores KIR2DL2/imunologia , Receptores KIR/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Feminino , Haplótipos/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Nat Commun ; 13(1): 866, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35165282

RESUMO

Epstein-Barr virus (EBV) is reportedly the first identified human tumor virus, and is closely related to the occurrence and development of nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), and several lymphomas. PD-L1 expression is elevated in EBV-positive NPC and GC tissues; however, the specific mechanisms underlying the EBV-dependent promotion of PD-L1 expression to induce immune escape warrant clarification. EBV encodes 44 mature miRNAs. In this study, we find that EBV-miR-BART11 and EBV-miR-BART17-3p upregulate the expression of PD-L1 in EBV-associated NPC and GC. Furthermore, EBV-miR-BART11 targets FOXP1, EBV-miR-BART17-3p targets PBRM1, and FOXP1 and PBRM1 bind to the enhancer region of PD-L1 to inhibit its expression. Therefore, EBV-miR-BART11 and EBV-miR-BART17-3p inhibit FOXP1 and PBRM1, respectively, and enhance the transcription of PD-L1 (CD274, http://www.ncbi.nlm.nih.gov/gene/29126 ), resulting in the promotion of tumor immune escape, which provides insights into potential targets for EBV-related tumor immunotherapy.


Assuntos
Herpesvirus Humano 4/genética , MicroRNAs/genética , Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Neoplasias Gástricas/imunologia , Evasão Tumoral/imunologia , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Infecções por Vírus Epstein-Barr/virologia , Fatores de Transcrição Forkhead/antagonistas & inibidores , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Herpesvirus Humano 4/imunologia , Humanos , Linfoma/imunologia , Linfoma/virologia , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/virologia , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/virologia , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Evasão Tumoral/genética , Microambiente Tumoral/imunologia
6.
Viruses ; 14(2)2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35215762

RESUMO

BACKGROUND: The aim of the present study was to evaluate the immunological profile of adult HIV-1+ patients coinfected with primary Epstein-Barr virus (EBV) infection who were free of antiretroviral drugs and inhabitants of the Brazilian Amazon region. MATERIALS AND METHODS: Primary EBV infection was screened by the semiquantitative detection of IgM and IgG anti-VCA. Genotypes were determined by conventional PCR. EBV and HIV viral load (VL) were quantified by real-time PCR. Cytokine dosage and cell quantification were performed by cytometry. RESULTS: Only HIV-1+ individuals had primary EBV infection (7.12%). The EBV-1 genotype was the most prevalent (47.37%). The VL of HIV-1 was lower in the HIV/EBV-2 group. CD4+ T lymphocytes were inversely proportional to the VL of EBV in HIV/EBV-1/2 multi-infected patients. The HIV/EBV-2 group had the lowest cytokine levels, especially IFN-γ and IL-4. Different correlations were proposed for each coinfection. The late search for specific care related to HIV infection directly affected the cytokine profile and the number of CD8+ T lymphocytes. Symptoms were associated with the increase in VL of both viruses and cytokine profile. CONCLUSIONS: Different immunological profiles were associated with EBV genotypes in primary infection, with EBV-2 being more frequent in patients with low levels of HIV viral load. With late infection monitoring and consequent delay in the initiation of HAART, clinical changes and effects on the maintenance of the immune response were observed.


Assuntos
Infecções por Vírus Epstein-Barr/virologia , Infecções por HIV/imunologia , HIV-1/imunologia , Herpesvirus Humano 4/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Coinfecção , Estudos Transversais , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/patologia , Feminino , Genótipo , Infecções por HIV/virologia , Soropositividade para HIV , Herpesvirus Humano 4/imunologia , Humanos , Imunidade , Masculino , Pessoa de Meia-Idade , Carga Viral , Adulto Jovem
9.
Medicine (Baltimore) ; 101(2): e28542, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029211

RESUMO

RATIONALE: Systemic forms of chronic active Epstein-Barr virus infection (CAEBV) can predispose a patient to a protracted course of fulminant hemophagocytic lymphohistiocytosis, which has a poor prognosis. Epstein-Barr virus (EBV) infection may persist even after theoretically curative hematopoietic stem cell transplantation. PATIENT CONCERNS: A female patient with CAEBV underwent chemotherapy followed by allogeneic hematopoietic stem cell transplantation from her human leukocyte antigen-matched sister. Neutrophil and platelet engraftment was observed on day +12 and +10. Full donor chimerism (DC) was achieved on Day +21. DIAGNOSES: From day +38, EBV-DNA in the blood was persistently positive, and DC declined. We attempted empirical interventions such as withdrawal of immune suppression, multiple donor lymphocyte infusion, stem cell boost, and interferon-α treatment. However, EBV-DNA copies continued to increase aggressively, whereas DC decreased rapidly and then reached a nadir of 63.27%. INTERVENTIONS: Salvage programmed death 1 (PD-1) antibody treatment was administered as salvage therapy at +69 and +84. OUTCOMES: EBV-DNA was negative on day +97 and was ultimately undetectable. Equivalently, a full and stable DC was obtained at +97. LESSONS: We summarize a case of PD-1 antibody used as salvage treatment in a post-transplant patient with CAEBV, which was eradicated and full DC was obtained. This case suggests that the PD-1 antibody appears to be a promising option for fighting EBV and mixed DCs.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Quimerismo/efeitos dos fármacos , Infecções por Vírus Epstein-Barr/complicações , Transplante de Células-Tronco Hematopoéticas , Receptor de Morte Celular Programada 1/uso terapêutico , Adulto , Infecções por Vírus Epstein-Barr/terapia , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 4/imunologia , Humanos
10.
Science ; 375(6578): 296-301, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35025605

RESUMO

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system of unknown etiology. We tested the hypothesis that MS is caused by Epstein-Barr virus (EBV) in a cohort comprising more than 10 million young adults on active duty in the US military, 955 of whom were diagnosed with MS during their period of service. Risk of MS increased 32-fold after infection with EBV but was not increased after infection with other viruses, including the similarly transmitted cytomegalovirus. Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion. These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/epidemiologia , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/virologia , Idade de Início , Anticorpos Antivirais/sangue , Biomarcadores/sangue , Estudos de Coortes , Citomegalovirus/imunologia , Feminino , Herpesvirus Humano 4/imunologia , Humanos , Estudos Longitudinais , Masculino , Militares , Esclerose Múltipla/etiologia , Proteínas de Neurofilamentos/sangue , Prevalência , Fatores de Risco , Adulto Jovem
12.
Nat Commun ; 13(1): 187, 2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-35039491

RESUMO

Epstein-Barr virus (EBV) persists in human B-cells by maintaining its chromatinized episomes within the nucleus. We have previously shown that cellular factor Poly [ADP-ribose] polymerase 1 (PARP1) binds the EBV genome, stabilizes CTCF binding at specific loci, and that PARP1 enzymatic activity correlates with maintaining a transcriptionally active latency program. To better understand PARP1's role in regulating EBV latency, here we functionally characterize the effect of PARP enzymatic inhibition on episomal structure through in situ HiC mapping, generating a complete 3D structure of the EBV genome. We also map intragenomic contact changes after PARP inhibition to global binding of chromatin looping factors CTCF and cohesin across the EBV genome. We find that PARP inhibition leads to fewer total unique intragenomic interactions within the EBV episome, yet new chromatin loops distinct from the untreated episome are also formed. This study also illustrates that PARP inhibition alters gene expression at the regions where chromatin looping is most effected. We observe that PARP1 inhibition does not alter cohesin binding sites but does increase its frequency of binding at those sites. Taken together, these findings demonstrate that PARP has an essential role in regulating global EBV chromatin structure and latent gene expression.


Assuntos
Proteínas de Ciclo Celular/genética , Cromatina/química , Proteínas Cromossômicas não Histona/genética , Mapeamento Cromossômico/métodos , Genoma Viral , Herpesvirus Humano 4/genética , Poli(ADP-Ribose) Polimerase-1/genética , Linfócitos B/patologia , Linfócitos B/virologia , Fator de Ligação a CCCTC/metabolismo , Proteínas de Ciclo Celular/metabolismo , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Infecções por Vírus Epstein-Barr/virologia , Regulação da Expressão Gênica , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/crescimento & desenvolvimento , Herpesvirus Humano 4/imunologia , Interações Hospedeiro-Patógeno , Humanos , Modelos Moleculares , Ftalazinas/farmacologia , Piperazinas/farmacologia , Plasmídeos/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Ligação Proteica , Transdução de Sinais , Transcrição Genética , Latência Viral/genética
16.
Virology ; 566: 136-142, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34922257

RESUMO

High mobility group box 1 (HMGB1) is an important chromatin protein and a pro-inflammatory molecule. Though shown to enhance target DNA binding by the Epstein-Barr virus (EBV) lytic switch protein ZEBRA, whether HMGB1 actually contributes to gammaherpesvirus biology is not known. In investigating the contribution of HMGB1 to the lytic phase of EBV, important for development of EBV-mediated diseases, we find that compared to latently-infected cells, lytic phase Burkitt lymphoma-derived cells and peripheral blood lytic cells during primary EBV infection express high levels of HMGB1. Our experiments place HMGB1 upstream of ZEBRA and reveal that HMGB1, through the NLRP3 inflammasome, sustains the expression of ZEBRA. These findings indicate that in addition to the NLRP3 inflammasome's recently discovered role in turning the EBV lytic switch on, NLRP3 cooperates with the danger molecule HMGB1 to also maintain ZEBRA expression, thereby sustaining the lytic signal.


Assuntos
Linfoma de Burkitt/genética , Infecções por Vírus Epstein-Barr/genética , Proteína HMGB1/genética , Herpesvirus Humano 4/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Transativadores/genética , Linfócitos B/imunologia , Linfócitos B/virologia , Linfoma de Burkitt/imunologia , Linfoma de Burkitt/patologia , Linfoma de Burkitt/virologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Regulação Neoplásica da Expressão Gênica , Proteína HMGB1/imunologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Inflamassomos/genética , Inflamassomos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Cultura Primária de Células , Transdução de Sinais , Transativadores/imunologia , Ativação Viral/genética , Ativação Viral/imunologia , Latência Viral/genética , Latência Viral/imunologia
17.
Br J Radiol ; 95(1130): 20210635, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34919440

RESUMO

OBJECTIVE: The purpose of this study is to evaluate the value of fluorine-18-fludeoxyglucose positron emission tomography (18F-FDG PET)/CT in the diagnosis and treatment evaluation of ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: 70 patients with OAML who received radiotherapy were recruited in our study. All the patients had the 18F-FDG PET/CT examination before the treatment. We retrospectively reviewed the medical records, pathological reports, laboratory results, and imaging features of all patients. The associations between 18F-FDG PET/CT parameters and Epstein-Barr virus antibodies, treatment response, MRI data, and Ki-67 expression were investigated. RESULTS: The PET/CT scan indicated that 80% (56/70) of the patients showed orbital FDG avidity. The median level of maximum standardized uptake value (SUVmax) of the lesions was 4.65 ± 3.00 (range:1.2-13.5). 92.0% (46/50) of the mass-forming lesions showed 18F-FDG avidity, while only 50.0% (10/20) of the non-massive lesions had 18F-FDG avidity (χ2 = 13.23, p=0.01). The SUVmax in orbit, conjunctiva, and lacrimal gland lymphoma were 5.6, 2.9, and 3.7, respectively. A significant difference was identified of SUVmax among the three locations' lymphoma using one-way ANOVA analysis (F = 5.039, p = 0.01). After completion of radiotherapy, the complete remission rate was achieved in 30.8% (4/13) of the patients without 18F-FDG avidity, and 70.4% (38/54) in cases with 18F-FDG avidity (χ2 = 5.43, p = 0.02). The correlation between high Ki-67 score and 18F-FDG avidity was confirmed (χ2 = 3.916, p = 0.048); however, no significant correlation was found between the SUVmax and Ki-67 score of the lesions (p = 0.971). Three patients (3/70, 4.3%) were upregulated the stage via PET/CT. CONCLUSION: 18F-FDG PET/CT had some potential values in the diagnosis and assessment of treatment response in patients with OAML. ADVANCES IN KNOWLEDGE: The value of 18F-FDG PET/CT for patients with OAML.


Assuntos
Neoplasias Oculares/diagnóstico por imagem , Fluordesoxiglucose F18/farmacocinética , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/análise , Túnica Conjuntiva/diagnóstico por imagem , Túnica Conjuntiva/metabolismo , Infecções por Vírus Epstein-Barr/imunologia , Neoplasias Oculares/metabolismo , Neoplasias Oculares/radioterapia , Feminino , Herpesvirus Humano 4/imunologia , Humanos , Antígeno Ki-67/análise , Aparelho Lacrimal/diagnóstico por imagem , Aparelho Lacrimal/metabolismo , Linfoma de Zona Marginal Tipo Células B/metabolismo , Linfoma de Zona Marginal Tipo Células B/radioterapia , Masculino , Pessoa de Meia-Idade , Órbita/diagnóstico por imagem , Órbita/metabolismo , Indução de Remissão , Estudos Retrospectivos
18.
Sci Rep ; 11(1): 23664, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34880297

RESUMO

Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy that has been etiologically linked to Epstein-Barr virus (EBV) infection, with EBV gene transcripts identified in almost all cases. However, the humoral immune response to EBV in NKTCL patients has not been well characterized. We examined the antibody response to EBV in plasma samples from 51 NKTCL cases and 154 controls from Hong Kong and Taiwan who were part of the multi-center, hospital-based AsiaLymph case-control study. The EBV-directed serological response was characterized using a protein microarray that measured IgG and IgA antibodies against 202 protein sequences representing the entire EBV proteome. We analyzed 157 IgG antibodies and 127 IgA antibodies that fulfilled quality control requirements. Associations between EBV serology and NKTCL status were disproportionately observed for IgG rather than IgA antibodies. Nine anti-EBV IgG responses were significantly elevated in NKTCL cases compared with controls and had ORshighest vs. lowest tertile > 6.0 (Bonferroni-corrected P-values < 0.05). Among these nine elevated IgG responses in NKTCL patients, three IgG antibodies (all targeting EBNA3A) are novel and have not been observed for other EBV-associated tumors of B-cell or epithelial origin. IgG antibodies against EBNA1, which have consistently been elevated in other EBV-associated tumors, were not elevated in NKTCL cases. We characterize the antibody response against EBV for patients with NKTCL and identify IgG antibody responses against six distinct EBV proteins. Our findings suggest distinct serologic patterns of this NK/T-cell lymphoma compared with other EBV-associated tumors of B-cell or epithelial origin.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade Humoral , Linfoma Extranodal de Células T-NK/etiologia , Proteínas Virais/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , Estudos de Casos e Controles , Suscetibilidade a Doenças , Ensaio de Imunoadsorção Enzimática , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Hong Kong , Humanos , Imunoglobulina G/imunologia , Linfoma Extranodal de Células T-NK/patologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Análise Serial de Proteínas , Taiwan , Proteínas Virais/metabolismo , Adulto Jovem
19.
PLoS Pathog ; 17(12): e1010137, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34882759

RESUMO

Epstein Barr Virus (EBV) infects more than 95% of the population whereupon it establishes a latent infection of B-cells that persists for life under immune control. Primary EBV infection can cause infectious mononucleosis (IM) and long-term viral carriage is associated with several malignancies and certain autoimmune diseases. Current efforts developing EBV prophylactic vaccination have focussed on neutralising antibodies. An alternative strategy, that could enhance the efficacy of such vaccines or be used alone, is to generate T-cell responses capable of recognising and eliminating newly EBV-infected cells before the virus initiates its growth transformation program. T-cell responses against the EBV structural proteins, brought into the newly infected cell by the incoming virion, are prime candidates for such responses. Here we show the structural EBV capsid proteins BcLF1, BDLF1 and BORF1 are frequent targets of T-cell responses in EBV infected people, identify new CD8+ and CD4+ T-cell epitopes and map their HLA restricting alleles. Using T-cell clones we demonstrate that CD4+ but not CD8+ T-cell clones specific for the capsid proteins can recognise newly EBV-infected B-cells and control B-cell outgrowth via cytotoxicity. Using MHC-II tetramers we show a CD4+ T-cell response to an epitope within the BORF1 capsid protein epitope is present during acute EBV infection and in long-term viral carriage. In common with other EBV-specific CD4+ T-cell responses the BORF1-specific CD4+ T-cells in IM patients expressed perforin and granzyme-B. Unexpectedly, perforin and granzyme-B expression was sustained over time even when the donor had entered the long-term infected state. These data further our understanding of EBV structural proteins as targets of T-cell responses and how CD4+ T-cell responses to EBV change from acute disease into convalescence. They also identify new targets for prophylactic EBV vaccine development.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Proteínas de Ligação a DNA/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Infecção Latente/imunologia , Linfócitos T Citotóxicos/imunologia , Proteínas Virais/imunologia , Herpesvirus Humano 4/imunologia , Humanos , Latência Viral/imunologia
20.
Front Immunol ; 12: 656797, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867935

RESUMO

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) affects approximately 1% of the general population. It is a chronic, disabling, multi-system disease for which there is no effective treatment. This is probably related to the limited knowledge about its origin. Here, we summarized the current knowledge about the pathogenesis of ME/CFS and revisit the immunopathobiology of Epstein-Barr virus (EBV) infection. Given the similarities between EBV-associated autoimmune diseases and cancer in terms of poor T cell surveillance of cells with EBV latency, expanded EBV-infected cells in peripheral blood and increased antibodies against EBV, we hypothesize that there could be a common etiology generated by cells with EBV latency that escape immune surveillance. Albeit inconclusive, multiple studies in patients with ME/CFS have suggested an altered cellular immunity and augmented Th2 response that could result from mechanisms of evasion to some pathogens such as EBV, which has been identified as a risk factor in a subset of ME/CFS patients. Namely, cells with latency may evade the immune system in individuals with genetic predisposition to develop ME/CFS and in consequence, there could be poor CD4 T cell immunity to mitogens and other specific antigens, as it has been described in some individuals. Ultimately, we hypothesize that within ME/CFS there is a subgroup of patients with DRB1 and DQB1 alleles that could confer greater susceptibility to EBV, where immune evasion mechanisms generated by cells with latency induce immunodeficiency. Accordingly, we propose new endeavors to investigate if anti-EBV therapies could be effective in selected ME/CFS patients.


Assuntos
Infecções por Vírus Epstein-Barr/etiologia , Síndrome de Fadiga Crônica/etiologia , Herpesvirus Humano 4/patogenicidade , Antígenos Virais/imunologia , Linfócitos B/imunologia , Linfócitos B/virologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Síndrome de Fadiga Crônica/imunologia , Síndrome de Fadiga Crônica/virologia , Predisposição Genética para Doença , Antígenos HLA-D/imunologia , Herpesvirus Humano 4/imunologia , Humanos , Imunidade Celular , Ativação Linfocitária , Modelos Imunológicos
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