RESUMO
Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease affecting the central nervous system (CNS) in animals that parallels several clinical and molecular traits of multiple sclerosis in humans. Herpes simplex virus type 1 (HSV-1) infection mainly causes cold sores and eye diseases, yet eventually, it can also reach the CNS, leading to acute encephalitis. Notably, a significant proportion of healthy individuals are likely to have asymptomatic HSV-1 brain infection with chronic brain inflammation due to persistent latent infection in neurons. Because cellular senescence is suggested as a potential factor contributing to the development of various neurodegenerative disorders, including multiple sclerosis, and viral infections may induce a premature senescence state in the CNS, potentially increasing susceptibility to such disorders, here we examine the presence of senescence-related markers in the brains and spinal cords of mice with asymptomatic HSV-1 brain infection, EAE, and both conditions. Across all scenarios, we find a significant increases of senescence biomarkers in the CNS with some differences depending on the analyzed group. Notably, some senescence biomarkers are exclusively observed in mice with the combined conditions. These results indicate that asymptomatic HSV-1 brain infection and EAE associate with a significant expression of senescence biomarkers in the CNS.
Assuntos
Encéfalo , Senescência Celular , Herpes Simples , Herpesvirus Humano 1 , Esclerose Múltipla , Animais , Camundongos , Encéfalo/virologia , Encéfalo/patologia , Encéfalo/metabolismo , Esclerose Múltipla/virologia , Esclerose Múltipla/patologia , Esclerose Múltipla/metabolismo , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 1/patogenicidade , Herpes Simples/virologia , Herpes Simples/patologia , Feminino , Camundongos Endogâmicos C57BL , Encefalomielite Autoimune Experimental/virologia , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/metabolismo , Fenótipo , Sistema Nervoso Central/virologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Medula Espinal/virologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Biomarcadores/metabolismo , Encefalite por Herpes Simples/virologia , Encefalite por Herpes Simples/patologia , Encefalite por Herpes Simples/metabolismoRESUMO
El virus de Epstein-Barr (VEB) fue el primer virus asociado a neoplasias en humanos. Infecta el 95 % de la población mundial, y aunque usualmente es asintomático, puede causar mononucleosis infecciosa y se relaciona con más de 200.000 casos de neoplasias al año. De igual forma, se asocia con esclerosis múltiple y otras enfermedades autoinmunes. A pesar de ser catalogado como un virus oncogénico, solo un pequeño porcentaje de los individuos infectados desarrollan neoplasias asociadas a VEB. Su persistencia involucra la capacidad de alternar entre una serie de programas de latencia, y de reactivarse cuando tiene la necesidad de colonizar nuevas células B de memoria, con el fin de sostener una infección de por vida y poder transmitirse a nuevos hospederos. En esta revisión se presentan las generalidades del VEB, además de su asociación con varios tipos de neoplasias, como son el carcinoma nasofaríngeo, el carcinoma gástrico, el linfoma de Hodgkin y el linfoma de Burkitt, y la esclerosis múltiple. Adicionalmente, se describen los mecanismos fisiopatológicos de las diferentes entidades, algunos de ellos no completamente dilucidados
Epstein-Barr virus (EBV) was the first virus associated with human cancer. It infects 95% of the world's population, and although it is usually asymptomatic, it causes infectious mononucleosis. It is related to more than 200,000 cases of cancer per year, and is also associated with multiple sclerosis and other autoimmune diseases. Despite being classified as an oncogenic virus, only a small percentage of infected individuals develop EBV-associated cancer. Its persistence involves the ability to alternate between a series of latency programs, and the ability to reactivate itself when it needs to colonize new memory B cells, in order to sustain a lifelong infection and be able to transmit to new hosts. In this review, the general characteristics of EBV are presented, in addition to its association with various types of cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma, and multiple sclerosis. Additionally, the pathophysiological mechanisms of the different entities are described, some of them not completely elucidated yet
Assuntos
Humanos , Herpesvirus Humano 4/fisiologia , Infecções por Vírus Epstein-Barr/complicações , Neoplasias Gástricas/fisiopatologia , Neoplasias Gástricas/virologia , Doença de Hodgkin/fisiopatologia , Doença de Hodgkin/virologia , Neoplasias Nasofaríngeas/fisiopatologia , Neoplasias Nasofaríngeas/virologia , Linfoma de Burkitt/fisiopatologia , Linfoma de Burkitt/virologia , Carcinogênese , Carcinoma Nasofaríngeo/fisiopatologia , Carcinoma Nasofaríngeo/virologia , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/virologiaRESUMO
Th17 cells are recognized as indispensable in inducing protective immunity against bacteria and fungi, as they promote the integrity of mucosal epithelial barriers. It is believed that Th17 cells also play a central role in the induction of autoimmune diseases. Recent advances have evaluated Th17 effector functions during viral infections, including their critical role in the production and induction of pro-inflammatory cytokines and in the recruitment and activation of other immune cells. Thus, Th17 is involved in the induction both of pathogenicity and immunoprotective mechanisms seen in the host's immune response against viruses. However, certain Th17 cells can also modulate immune responses, since they can secrete immunosuppressive factors, such as IL-10; these cells are called non-pathogenic Th17 cells. Here, we present a brief review of Th17 cells and highlight their involvement in some virus infections. We cover these notions by highlighting the role of Th17 cells in regulating the protective and pathogenic immune response in the context of viral infections. In addition, we will be describing myocarditis and multiple sclerosis as examples of immune diseases triggered by viral infections, in which we will discuss further the roles of Th17 cells in the induction of tissue damage.
Assuntos
Miocardite/imunologia , Células Th17/metabolismo , Viroses/imunologia , Adenoviridae , Animais , Doenças Autoimunes/imunologia , Vírus Chikungunya , Citocinas/imunologia , Vírus da Dengue , Humanos , Sistema Imunitário , Imunossupressores/farmacologia , Inflamação , Interleucina-10/biossíntese , Linfócitos/citologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/metabolismo , Esclerose Múltipla/virologia , Miocardite/metabolismo , Miocardite/virologia , Orthomyxoviridae , SARS-CoV-2 , Simplexvirus , Células Th1/citologia , Células Th2/citologia , Viroses/tratamento farmacológico , Viroses/metabolismo , Zika virusRESUMO
The chronic dysfunction of neuronal cells, both central and peripheral, a characteristic of neurological disorders, may be caused by irreversible damage and cell death. In 2016, more than 276 million cases of neurological disorders were reported worldwide. Moreover, neurological disorders are the second leading cause of death. Generally, the etiology of neurological diseases is not fully understood. Recent studies have related the onset of neurological disorders to viral infections, which may cause neurological symptoms or lead to immune responses that trigger these pathological signs. Currently, this relationship is mostly based on epidemiological data on infections and seroprevalence of patients who present with neurological disorders. The number of studies aiming to elucidate the mechanism of action by which viral infections may directly or indirectly contribute to the development of neurological disorders has been increasing over the years but these studies are still scarce. Comprehending the pathogenesis of these diseases and exploring novel theories may favor the development of new strategies for diagnosis and therapy in the future. Therefore, the objective of the present study was to review the main pieces of evidence for the relationship between viral infection and neurological disorders such as Alzheimer's disease, Parkinson's disease, Guillain-Barré syndrome, multiple sclerosis, and epilepsy. Viruses belonging to the families Herpesviridae, Orthomyxoviridae, Flaviviridae, and Retroviridae have been reported to be involved in one or more of these conditions. Also, neurological symptoms and the future impact of infection with SARS-CoV-2, a member of the family Coronaviridae that is responsible for the COVID-19 pandemic that started in late 2019, are reported and discussed.
Assuntos
COVID-19/patologia , Doenças do Sistema Nervoso/virologia , Tropismo Viral/fisiologia , Doença de Alzheimer/virologia , COVID-19/virologia , Epilepsia/virologia , Flaviviridae/metabolismo , Síndrome de Guillain-Barré/virologia , Herpesviridae/metabolismo , Humanos , Esclerose Múltipla/virologia , Doenças do Sistema Nervoso/patologia , Orthomyxoviridae/metabolismo , Doença de Parkinson/virologia , Retroviridae/metabolismo , SARS-CoV-2/metabolismoRESUMO
An association between varicella zoster virus (VZV) and multiple sclerosis (MS) has been reported in Mexican populations. The aim of this study was to compare the response of T cells from MS patients, during relapse and remission, to in vitro stimulation with VZV, adenovirus (AV) and Epstein-Barr virus (EBV). Proliferation and cytokine secretion of T cells from 29 relapsing-remitting MS patients and 38 healthy controls (HC) were analyzed by flow cytometry after stimulating with VZV, AV or EBV. IgG and IgM levels against VZV and EBV were quantified using Enzyme-Linked Immunosorbent Assay. Relapsing MS patients showed a higher percentage of responding CD4+ and CD8+ T cells against VZV compared to AV. In HC and remitting MS patients, proliferation of CD4+ T cells was higher when stimulated with VZV as compared to EBV. Moreover, T cells isolated from remitting patients secreted predominantly Th1 cytokines when cell cultures were stimulated with VZV. Finally, high concentration of anti-VZV IgG was found in sera from patients and controls. The results support previous studies of an VZV-MS association in the particular population studied and provide additional information about the possible role of this virus in the pathogenesis of MS.
Assuntos
Herpesvirus Humano 3/fisiologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/virologia , Linfócitos T/imunologia , Adenoviridae/fisiologia , Adulto , Anticorpos Antivirais/imunologia , Citocinas/metabolismo , Feminino , Herpesvirus Humano 3/imunologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/fisiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Esclerose Múltipla Recidivante-Remitente/imunologia , Esclerose Múltipla Recidivante-Remitente/virologia , Recidiva , Indução de RemissãoAssuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla/terapia , Pneumonia Viral/imunologia , Adulto , Betacoronavirus/imunologia , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Tosse/diagnóstico , Tosse/fisiopatologia , Tosse/virologia , Ciclofosfamida/uso terapêutico , Dispneia/diagnóstico , Dispneia/fisiopatologia , Dispneia/virologia , Feminino , Febre/diagnóstico , Febre/fisiopatologia , Febre/virologia , Cefaleia/diagnóstico , Cefaleia/fisiopatologia , Cefaleia/virologia , Humanos , Masculino , México , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/imunologia , Esclerose Múltipla/virologia , Agonistas Mieloablativos/uso terapêutico , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Risco , Rituximab/uso terapêutico , SARS-CoV-2 , Condicionamento Pré-Transplante/métodos , Transplante AutólogoRESUMO
Treatment options for multiple sclerosis (MS) have changed over the last few years, bringing about a new category of drugs with more efficient profiles. However, these drugs have come with a whole new profile of potential adverse events that neurologists have to learn well and quickly. One of the most feared complications of these MS treatments is progressive multifocal leukoencephalopathy caused by the reactivation of the John Cunningham virus (JCV). OBJECTIVE: To identify the serologic profile of JCV in patients with MS. METHODS: Data on serum antibodies for JCV were obtained using the enzyme-linked immunosorbent assay provided by the STRATIFY-JCV program. RESULTS: A total of 1,501 blood tests were obtained from 1,102 patients with MS. There were 633 patients (57.1%) who were positive for antibodies for JCV and 469 patients who were negative (42.9%). Twenty-three patients became positive after initially having negative JCV antibody status. The rate of seroconversion was 18.5% over 22 months. CONCLUSION: The JCV serologic profile and seroconversion in Brazilian patients were similar to those described in other countries.
Assuntos
Anticorpos Antivirais/sangue , Vírus JC/imunologia , Leucoencefalopatia Multifocal Progressiva/imunologia , Esclerose Múltipla/virologia , Infecções por Polyomavirus/imunologia , Adulto , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Leucoencefalopatia Multifocal Progressiva/sangue , Masculino , Esclerose Múltipla/sangue , Esclerose Múltipla/tratamento farmacológico , Natalizumab/efeitos adversos , Infecções por Polyomavirus/epidemiologia , Prevalência , Soroconversão , Fatores SexuaisRESUMO
ABSTRACT Treatment options for multiple sclerosis (MS) have changed over the last few years, bringing about a new category of drugs with more efficient profiles. However, these drugs have come with a whole new profile of potential adverse events that neurologists have to learn well and quickly. One of the most feared complications of these MS treatments is progressive multifocal leukoencephalopathy caused by the reactivation of the John Cunningham virus (JCV). Objective: To identify the serologic profile of JCV in patients with MS. Methods: Data on serum antibodies for JCV were obtained using the enzyme-linked immunosorbent assay provided by the STRATIFY-JCV program. Results: A total of 1,501 blood tests were obtained from 1,102 patients with MS. There were 633 patients (57.1%) who were positive for antibodies for JCV and 469 patients who were negative (42.9%). Twenty-three patients became positive after initially having negative JCV antibody status. The rate of seroconversion was 18.5% over 22 months. Conclusion: The JCV serologic profile and seroconversion in Brazilian patients were similar to those described in other countries.
RESUMO As opções terapêuticas para esclerose múltipla (EM) modificaram-se ao longo dos últimos anos, trazendo uma nova categoria de drogas com melhor perfil de eficácia. No entanto, estas drogas vieram com um novo perfil de potenciais eventos adversos que exigem que o neurologista os reconheça bem e rapidamente. Uma das complicações mais temidas destes tratamentos para a EM é a leucoencefalopatia multifocal progressiva (LEMP), causada pela reativação do vírus John Cunningham (JCV). Objetivo: Identificar o perfil sorológico de JCV em pacientes com EM. Métodos: Dados sorológicos de JCV foram obtidos através do ensaio por enzimas imuno-adsorvidas (ELISA) fornecido pelo programa STRATIFY-JCV. Resultados: Um total de 1.501 testes sanguíneos foram obtidos de 1.102 pacientes com EM. O grupo teve 633 pacientes (57,1%) soropositivos para anticorpos anti-JCV e 469 pacientes negativos (42,9%). Vinte e três pacientes se tornaram posivitos após resultados iniciais negativos para anticorpos anti-JCV. A taxa de soroconversão foi 18,5% em 22 meses. Conclusão: O perfil sorológico do JCV e a soroconversão nos pacientes brasileiros foi semelhante àquela descrita em outros países.
Assuntos
Humanos , Masculino , Feminino , Adulto , Leucoencefalopatia Multifocal Progressiva/imunologia , Vírus JC/imunologia , Infecções por Polyomavirus/imunologia , Anticorpos Antivirais/sangue , Esclerose Múltipla/virologia , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Fatores Sexuais , Prevalência , Leucoencefalopatia Multifocal Progressiva/sangue , Infecções por Polyomavirus/epidemiologia , Natalizumab/efeitos adversos , Soroconversão , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/sangueRESUMO
Multiple sclerosis (MS) is a high prevalence degenerative disease characterized at the cellular level by glial and neuronal cell death. The causes of cell death during the disease course are not fully understood. In this work we demonstrate that in a MS model induced by Theiler's murine encephalomyelitis virus (TMEV) infection, the inward rectifier (Kir) 4.1 potassium channel subunit is overexpressed in astrocytes. In voltage clamp experiments the inward current density from TMEV-infected astrocytes was significantly larger than in mock-infected ones. The cRNA hybridization analysis from mock- and TMEV-infected cells showed an upregulation of a potassium transport channel coding sequence. We validated this mRNA increase by RT-PCR and quantitative PCR using Kir 4.1 specific primers. Western blotting experiments confirmed the upregulation of Kir 4.1, and alignment between sequences provided the demonstration that the over-expressed gene encodes for a Kir family member. Flow cytometry showed that the Kir 4.1 protein is located mainly in the cell membrane in mock and TMEV-infected astrocytes. Our results demonstrate an increase in K+ inward current in TMEV-infected glial cells, this increment may reduce the neuronal depolarization, contributing to cell resilience mechanisms.
Assuntos
Astrócitos/metabolismo , Esclerose Múltipla/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Animais , Infecções por Cardiovirus/complicações , Infecções por Cardiovirus/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Potenciais da Membrana , Mesocricetus , Esclerose Múltipla/virologia , RNA Mensageiro , Theilovirus/patogenicidade , Regulação para CimaRESUMO
OBJECTIVES: John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals. METHODS: The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: "JCV" OR "JC virus" AND "multiple sclerosis" OR "MS" OR "NMO" OR "neuromyelitis optica" AND "prevalence." These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase. RESULTS: After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%). CONCLUSIONS: The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.