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Nature Reviews. Neurology Mar 2023Epidemiological studies have provided compelling evidence that multiple sclerosis (MS) is a rare complication of infection with the Epstein-Barr virus (EBV), a... (Review)
Review
Epidemiological studies have provided compelling evidence that multiple sclerosis (MS) is a rare complication of infection with the Epstein-Barr virus (EBV), a herpesvirus that infects more than 90% of the global population. This link was long suspected because the risk of MS increases markedly after infectious mononucleosis (symptomatic primary EBV infection) and with high titres of antibodies to specific EBV antigens. However, it was not until 2022 that a longitudinal study demonstrated that MS risk is minimal in individuals who are not infected with EBV and that it increases over 30-fold following EBV infection. Over the past few years, a number of studies have provided clues on the underlying mechanisms, which might help us to develop more targeted treatments for MS. In this Review, we discuss the evidence linking EBV to the development of MS and the mechanisms by which the virus is thought to cause the disease. Furthermore, we discuss implications for the treatment and prevention of MS, including the use of antivirals and vaccines.
Topics: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Multiple Sclerosis; Longitudinal Studies; Antibodies, Viral
PubMed: 36759741
DOI: 10.1038/s41582-023-00775-5 -
Gastroenterology Clinics of North... Jun 2020Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections are common and are associated with a variety of liver manifestations. EBV and CMV infections, in... (Review)
Review
Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections are common and are associated with a variety of liver manifestations. EBV and CMV infections, in immunocompetent hosts, commonly manifest as acute hepatitis, with severity varying from asymptomatic, self-limited icteric hepatitis to acute liver failure. Atypical manifestations, such as cholestasis, chronic hepatitis, precipitation of acute-on-chronic liver failure, and autoimmune hepatitis, are reported with EBV infection, whereas cholestasis, portal vein thrombosis, and Budd-Chiari syndrome are reported with CMV infection. In the setting of liver transplantation, CMV is the most common infectious complication and carries significant morbidity; EBV is the major cause of post-transplant lymphoproliferative disorders.
Topics: Cytomegalovirus Infections; Epstein-Barr Virus Infections; Hepatitis, Viral, Human; Humans; Immunocompromised Host; Liver Transplantation; Lymphoproliferative Disorders; Postoperative Complications
PubMed: 32389366
DOI: 10.1016/j.gtc.2020.01.008 -
Viruses Nov 2021Epstein-Barr virus (EBV) is a causative agent of infectious mononucleosis and several types of cancer. Like other herpesviruses, it establishes an asymptomatic,... (Review)
Review
Epstein-Barr virus (EBV) is a causative agent of infectious mononucleosis and several types of cancer. Like other herpesviruses, it establishes an asymptomatic, life-long latent infection, with occasional reactivation and shedding of progeny viruses. During latency, EBV expresses a small number of viral genes, and exists as an episome in the host-cell nucleus. Expression patterns of latency genes are dependent on the cell type, time after infection, and milieu of the cell (e.g., germinal center or peripheral blood). Upon lytic induction, expression of the viral immediate-early genes, BZLF1 and BRLF1, are induced, followed by early gene expression, viral DNA replication, late gene expression, and maturation and egress of progeny virions. Furthermore, EBV reactivation involves more than just progeny production. The EBV life cycle is regulated by signal transduction, transcription factors, promoter sequences, epigenetics, and the 3D structure of the genome. In this article, the molecular basis of EBV latency establishment and reactivation is summarized.
Topics: Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Immediate-Early Proteins; Trans-Activators; Virus Activation; Virus Latency
PubMed: 34960613
DOI: 10.3390/v13122344 -
Viruses Feb 2023Epstein-Barr virus (EBV) is an oncogenic virus infecting more than 95% of the world's population. After primary infection-responsible for infectious mononucleosis in... (Review)
Review
Epstein-Barr virus (EBV) is an oncogenic virus infecting more than 95% of the world's population. After primary infection-responsible for infectious mononucleosis in young adults-the virus persists lifelong in the infected host, especially in memory B cells. Viral persistence is usually without clinical consequences, although it can lead to EBV-associated cancers such as lymphoma or carcinoma. Recent reports also suggest a link between EBV infection and multiple sclerosis. In the absence of vaccines, research efforts have focused on virological markers applicable in clinical practice for the management of patients with EBV-associated diseases. Nasopharyngeal carcinoma is an EBV-associated malignancy for which serological and molecular markers are widely used in clinical practice. Measuring blood EBV DNA load is additionally, useful for preventing lymphoproliferative disorders in transplant patients, with this marker also being explored in various other EBV-associated lymphomas. New technologies based on next-generation sequencing offer the opportunity to explore other biomarkers such as the EBV DNA methylome, strain diversity, or viral miRNA. Here, we review the clinical utility of different virological markers in EBV-associated diseases. Indeed, evaluating existing or new markers in EBV-associated malignancies or immune-mediated inflammatory diseases triggered by EBV infection continues to be a challenge.
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Lymphoma; Lymphoproliferative Disorders; Nasopharyngeal Neoplasms
PubMed: 36992365
DOI: 10.3390/v15030656 -
American Family Physician Sep 2021Splenomegaly can be due to several mechanisms but is almost always a sign of a systemic condition. Patient habits, travel, and medical conditions can increase risk of...
Splenomegaly can be due to several mechanisms but is almost always a sign of a systemic condition. Patient habits, travel, and medical conditions can increase risk of splenomegaly and suggest etiology. Symptoms can suggest infectious, malignant, hepatic, or hematologic causes. Physical examination will typically reveal splenomegaly, but abdominal ultrasonography is recommended for confirmation. Physical examination should also assess for signs of systemic illness, liver disease, and anemia or other hematologic issues. The most common causes of splenomegaly in the United States are liver disease, malignancy, and infection. Except for apparent causes such as infectious mononucleosis, basic laboratory analysis and ultrasonography are the first-line steps in determining etiology. Malaria and schistosomiasis are common in tropical regions, where as many as 80% of people may have splenomegaly. Management of splenomegaly involves treating the underlying disease process. Splenectomies and spleen reduction therapies are sometimes performed. Any patient with limited splenic function requires increased vaccination and prophylactic antibiotics for procedures involving the respiratory tract. Acute infections, anemia, and splenic rupture are the most common complications of splenomegaly, and people with splenomegaly should refrain from participating in contact sports to decrease risk of rupture.
Topics: Anemia; Disease Management; Humans; Splenic Rupture; Splenomegaly; Ultrasonography
PubMed: 34523897
DOI: No ID Found -
Infection and Drug Resistance 2023Epstein-Barr virus (EBV), a causative agent for several types of lymphomas and mucosal cancers, is a human lymphotropic herpesvirus with the capacity to establish... (Review)
Review
Epstein-Barr virus (EBV), a causative agent for several types of lymphomas and mucosal cancers, is a human lymphotropic herpesvirus with the capacity to establish lifelong latent infection. More than 90% of the human population worldwide is infected. The primary infection is usually asymptomatic in childhood, whereas infectious mononucleosis (IM) is common when the infection occurs in adolescence. Primary EBV infection, with or without IM, or reactivation of latent infection in immunocompromised individuals have been associated with a wide range of neurologic conditions, such as encephalitis, meningitis, acute disseminated encephalomyelitis, and cerebellitis. EBV is also involved in malignant lymphomas in the brain. An increasing number of reports on EBV-related disorders of the central nervous system (CNS) including the convincing association with multiple sclerosis (MS) have put in focus EBV-related conditions beyond its established link to malignancies. In this review, we present the clinical manifestations of EBV-related CNS-disorders, put them in the context of known EBV biology and focus on available treatment options and future therapeutic approaches.
PubMed: 37465179
DOI: 10.2147/IDR.S375624 -
Cell Reports. Medicine Jun 2022Epstein-Barr virus (EBV) is a cancer-associated pathogen responsible for 165,000 deaths annually. EBV is also the etiological agent of infectious mononucleosis and is...
Epstein-Barr virus (EBV) is a cancer-associated pathogen responsible for 165,000 deaths annually. EBV is also the etiological agent of infectious mononucleosis and is linked to multiple sclerosis and rheumatoid arthritis. Thus, an EBV vaccine would have a significant global health impact. EBV is orally transmitted and has tropism for epithelial and B cells. Therefore, a vaccine would need to prevent infection of both in the oral cavity. Passive transfer of monoclonal antibodies against the gH/gL glycoprotein complex prevent experimental EBV infection in humanized mice and rhesus macaques, suggesting that gH/gL is an attractive vaccine candidate. Here, we evaluate the immunogenicity of several gH/gL nanoparticle vaccines. All display superior immunogenicity relative to monomeric gH/gL. A nanoparticle displaying 60 copies of gH/gL elicits antibodies that protect against lethal EBV challenge in humanized mice, whereas antibodies elicited by monomeric gH/gL do not. These data motivate further development of gH/gL nanoparticle vaccines for EBV.
Topics: Animals; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Immunization; Macaca mulatta; Mice; Nanoparticles; Vaccines
PubMed: 35705092
DOI: 10.1016/j.xcrm.2022.100658 -
European Journal of Pediatrics Oct 2020In previously healthy subjects, vulvar ulcers are mostly caused by sexually transmitted microorganisms. Lipschütz's acute vulvar ulceration, first reported in 1912, is...
In previously healthy subjects, vulvar ulcers are mostly caused by sexually transmitted microorganisms. Lipschütz's acute vulvar ulceration, first reported in 1912, is a non-sexually acquired condition characterized by sudden onset of a few genital ulcers. We systematically review presentation, underlying causes, and disease duration of Lipschütz's ulceration. A comprehensive source of Excerpta Medica, National Library of Medicine, and Web of Science databases was performed. Reports including cases of apparently previously healthy females affected by Lipschütz's ulceration were selected. A predefined database was used to extract data on demographics, history, clinical and microbiological findings, and treatment.The search disclosed 158 cases. Almost 90% of cases were ≤ 20 years of age and sexually inactive. Lesions were usually one to about three, painful, ≥ 10 mm large, well-delimited, with a fibrinous and necrotic center and a symmetric distribution. Voiding disorders and enlarged inguinal lymph nodes were observed in a large subset of cases. Canker sores were noted in 10% of patients. Lipschütz's vulvar ulceration occurred concomitantly with an infectious disease in 139 cases. Infectious mononucleosis syndrome (N = 40) was the most frequently detected well-defined infection, followed by mycoplasma species infections (N = 11). The disease resolved after ≤ 3 weeks.Conclusions: Lipschütz's ulceration mainly affects both sexually inactive and, less frequently, sexually active subjects ≤ 20 years of age, presents with ≤ 3 vulvar ulcers, resolves without recurrences within 3 weeks and is temporarily associated with an infection, most frequently a flu-like illness or an infectious mononucleosis syndrome. What is Known: • Lipschütz's acute vulvar ulceration is a non-sexually acquired condition, which is characterized by a sudden onset of a few necrotic and painful genital ulcers. • The condition tends to resolve spontaneously and is usually triggered by an infection. What is New: • The condition mainly affects subjects ≤ 20 years of age, tends to resolve within 3 weeks, and is usually temporarily associated with a flu-like illness or an infectious mononucleosis syndrome. • Systemic corticosteroids do not reduce disease duration.
Topics: Diagnosis, Differential; Female; Humans; Infant, Newborn; Recurrence; Stomatitis, Aphthous; Ulcer; Vulvar Diseases
PubMed: 32296983
DOI: 10.1007/s00431-020-03647-y -
The New England Journal of Medicine Sep 2021
Topics: Amoxicillin; Child; Drug Eruptions; Exanthema; Female; Humans; Infectious Mononucleosis; Pharyngitis
PubMed: 34496177
DOI: 10.1056/NEJMicm2104358