Materiały źródłowe

• #1 Infectious Mononucleosis: Pathogenesis, Symptoms and Treatment | Medcrine Academy

  https://medcrine.com/infectious-mononucleosis

  Infectious mononucleosis is a self-limiting lymphoproliferative disorder caused by the Epstein-Barr virus (Human Herpes type 4), a member of the herpesvirus family. […] Infectious mononucleosis is largely transmitted through oral contact with EBV-contaminated saliva. […] The virus initially penetrates the nasopharyngeal, oropharyngeal, and salivary epithelial cells. It then spreads to the underlying oropharyngeal lymphoid tissue and, more specifically, to B lymphocytes, all of which have receptors for EBV. […] Infection of the B cells may take one of two forms; it may kill the infected B cell, or the virus may incorporate itself into the cells genome. […] The B cells that harbor the EBV genome proliferate in the circulation and produce the well-known heterophil antibodies that are used for the diagnosis of infectious mononucleosis.

• #1 Epstein-Barr Virus (EBV) Infectious Mononucleosis (Mono): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/222040-overview

  Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that causes lifelong infections in humans. It is primarily spread through intimate contact with oropharyngeal secretions, though it can also be transmitted via genital secretions, blood transfusions, and organ transplants. Upon initial infection, EBV specifically targets B lymphocytes in the oropharyngeal epithelium. Following this acute phase, the virus can persist in oropharyngeal secretions for up to 32 weeks and remain in the body for decades. […] Once EBV infects B lymphocytes, atypical lymphocytes develop, primarily from CD8+ T cells that respond to the viral infection. After the primary infection, EBV remains dormant in the host, mainly within B lymphocytes, and undergoes intermittent asymptomatic shedding from the oropharynx. In healthy adults who are EBV-seropositive, the virus can be detected in the oropharyngeal secretions of 10-20% of individuals. This shedding is more frequent and at higher levels in immunocompromised patients, such as organ transplant recipients and individuals living with HIV.

• #1 Mononucleosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470387/

  When EBV is introduced into the oropharynx, the virus begins the replication process. There is a predilection for infection of the B-cells of lymphoid tissue. Subsequently, the infection spreads through the lymphatic system. The body reacts by developing antibodies against the virus. In 90% or more of cases, heterophile antibodies are produced in response to the infection with EBV. EBV is a lifelong infection with periodic reactivation. In poor immune response systems, there is a small risk of EBV-induced malignancy, such as Hodgkin lymphoma.[5][6] […] After exposure, the EBV infects the epithelial cells of the salivary glands and the oropharynx. Lymphocytes residing in the tonsils get exposed to the virus and then enter the bloodstream. Lymphoid hyperplasia is common and may be seen as generalized lymphadenopathy, tonsillitis, and hepatosplenomegaly.

• #1 How EBV Infects: The Tropism and Underlying Molecular Mechanism for Viral Infection

  https://www.mdpi.com/1999-4915/14/11/2372

  The Epstein–Barr virus (EBV) is associated with a variety of human malignancies, including Burkitt’s lymphoma, Hodgkin’s disease, nasopharyngeal carcinoma and gastric cancers. EBV infection is crucial for the oncogenesis of its host cells. The prerequisite for the establishment of infection is the virus entry. Interactions of viral membrane glycoproteins and host membrane receptors play important roles in the process of virus entry into host cells. […] The entry machine of the EBV is highly sophisticated, enabling its infection of different cell types. As many as 13 glycoproteins are encoded by EBV, with eleven of them found on the virion envelope, and the entry process requires the coordination of multiple glycoproteins. […] Understanding how EBV establishes variable host tropisms and the underlying mechanism for EBV entry into different cell types could be the cornerstone for developing prophylactic vaccines and therapeutic agents against EBV infection in all kinds of susceptible cells.

• #1 Infectious Mononucleosis (EBV)

  https://www.atsu.edu/faculty/chamberlain/website/lectures/lecture/mono.htm

  Epithelial cells of the oropharynx are the portals of EBV infection. The virus is transmitted primarily by repeated contact with oropharyngeal secretions, and is primarily transmitted by adults 30-50 days or by children 10-14 days following infection. It can be isolated from saliva, blood, and lymphatics. EBV invades B lymphocytes by means of their CD21 receptors; within 18-24 hours, EBV antigens are detectable within the lymphocyte nucleus. […] The signs and symptoms of infectious mononucleosis are the result of viral replication and the host immune response to viral antigens. Infected B lymphocytes spread the infection throughout the reticuloendothelial system (e.g., liver, spleen, and peripheral lymph nodes). EBV infection of B lymphocytes results in a humoral and cellular response to the virus. EBV initiates B lymphocyte proliferation (plasma cells) and immortalization (memory B lymphocyte) without the role of T-helper cells. EBV is a B-cell mitogen that can cause many B lymphocytes to become antibody-producing plasma cells.

• #1 Infectious Mononucleosis (EBV)

  https://www.atsu.edu/faculty/chamberlain/website/lectures/lecture/mono.htm

  Many of the antibody-producing plasma cells produce antibodies that do not react with EBV antigens. Some of the plasma cells produce antibodies that react with red blood cells from other mammals such as cattle and sheep. This humoral immune response, called the heterophile response, is the basis for the serologic tests used to screen for infectious mononucleosis (e.g., heterophil antibody test [Monospot test]). Other plasma cells produce antibodies that react with EBV antigens and can be used to confirm a diagnosis of infectious mononucleosis. As with many viral infections, the T lymphocyte response is essential in the control of EBV infection; natural killer (NK) cells and predominantly CD8 cytotoxic T cells control proliferating B lymphocytes infected with EBV. […] During the acute phase of infectious mononucleosis, as many as 20% of the circulating B lymphocytes will produce EBV antigens, whereas only 1% will produce them during convalescence. The virus usually is not found free in the blood but is present as immune complexes, which may be responsible for the arthralgias and urticarial rashes that occur during the acute phase of the disease.

• #1 Infectious Mononucleosis (EBV)

  https://www.atsu.edu/faculty/chamberlain/website/lectures/lecture/mono.htm

  B lymphocytes that produce complete virions are killed by viral-directed cytolysis, whereas infected B lymphocytes that do not produce complete virions are the target of cytotoxic T cells that control their proliferation. Lymphocytosis associated with infectious mononucleosis is caused by an increase in the number of circulating activated T and B lymphocytes. CD8+ T- cells increase in numbers in the blood stream and are activated (also known as Downey cells, reactive lymphocytes or atypical lymphocytes because of their atypical presence in peripheral blood) to eliminate EBV infected B- lymphocytes. EBV can be recovered from oropharyngeal washings 12-18 months after the disappearance of circulating Downey cells and the patient has recovered from the illness. Infection with the EBV virus is lifelong.

• #1 Epstein-Barr Virus (EBV) Infectious Mononucleosis (Mono): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/784513-overview

  The immune response to EBV infection often results in fever (due to cytokine release), lymphocytosis (caused by EBV-infected B-cell proliferation in the reticuloendothelial system), and pharyngitis (from lymphatic tissue proliferation in the oropharynx). […] EBV exhibits a biphasic lifecycle, alternating between latent and lytic phases. During latency, EBV maintains its genome as an episome within B lymphocytes, particularly memory B cells, allowing it to persist while evading immune detection by suppressing viral gene expression. Reactivation from latency into the lytic phase can occur under conditions such as immunosuppression or psychological stress, leading to viral replication and potential disease manifestations. […] EBV’s ability to evade immune surveillance, transform host cells, and potentially integrate into the genome underpins its association with various malignancies, autoimmune conditions, and chronic diseases like chronic fatigue syndrome. Insights into its genomic diversity, lifecycle, and host interactions provide critical opportunities for therapeutic interventions, including vaccines and targeted antiviral therapies.

• #1 Epstein-Barr Virus (EBV) Infectious Mononucleosis (Mono): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/222040-overview

  The immune response to EBV infection often results in fever (due to cytokine release), lymphocytosis (caused by EBV-infected B-cell proliferation in the reticuloendothelial system), and pharyngitis (from lymphatic tissue proliferation in the oropharynx). […] EBV exhibits a biphasic lifecycle, alternating between latent and lytic phases. During latency, EBV maintains its genome as an episome within B lymphocytes, particularly memory B cells, allowing it to persist while evading immune detection by suppressing viral gene expression. Reactivation from latency into the lytic phase can occur under conditions such as immunosuppression or psychological stress, leading to viral replication and potential disease manifestations. […] Studies have highlighted the intra-host genomic diversity of EBV and its potential integration into the host genome. While EBV typically persists episomally, instances of viral integration have been observed, particularly in malignancies like mantle cell lymphoma.

• #1 Epstein-Barr virus infection: the micro and macro worlds | Virology Journal | Full Text

  https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02187-9

  EBV infection is divided into three main phases: primary infection and lytic replication, latency and lytic reactivation. […] After primary infection, the virus remains dormant, with memory B cells serving as the main reservoir of their persistence. […] EBV can maintain in the latent infection phase in the human host, which is an important reason why the virus cannot be eradicated and can maintain lifelong persistence. […] During the latent infection phase, EBV expresses only a limited subset of viral genes and noncoding RNAs, including six nuclear antigens, EBNA-1, EBNA-2, EBNA-3 A, EBNA-3B, EBNA-3 C, and LP; three latent membrane proteins (LMPs), LMP-1 and LMP-2 A/B; and two types of non-coding RNA that are not translated into proteins, EBV-encoded RNAs (EBERs) and microRNAs (miRNAs).

• #1 Epstein-Barr virus infection: the micro and macro worlds | Virology Journal | Full Text

  https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02187-9

  Infected memory B cells in the latent infection phase are occasionally reactivated and differentiated into plasma cells, which can induce EBV reactivation after cytolysis, thereby entering the lytic reactivation phase from the latent infection phase. […] The expression of BZLF1 and BRLF1 in the latent phase is inhibited by a variety of cellular transcriptional repressors. […] The pathogenic mechanism underlying EBV infection is complex and can affect various systems, exhibiting a variety of atypical clinical symptoms and signs and leading to various benign or malignant diseases.

• #1 The Pathogenesis of Epstein-Barr Virus Persistent Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3789532/

  Epstein-Barr virus (EBV) maintains a lifelong infection. According to the germinal center model (GCM), latently infected B cells transit the germinal center (GC) to become resting memory cells. […] The GCM remains the only model that explains EBV biology and the pathogenesis of lymphoma. Recent work suggests modifications to the model notably that the virus contributes only modestly to the GC process and predictions from mathematical models that quiescence within memory B cells shapes the overall structure of viral infection but is not essential for persistence. […] The GCM proposes that EBV persists by exploiting normal B cell biology. This involves the virus passing through a cycle of infected stages, each employing a discrete viral gene transcription program. […] Thus, the GCM accounts for all the latent and lytic stages of the virus and thereby provides an explanation for the origin of EBV-associated lymphomas.

• #1 Epstein–Barr Virus History and Pathogenesis

  https://www.mdpi.com/1999-4915/15/3/714

  The fact that EBV persists for the lifetime of the host indicates that it has evolved successful strategies to obstruct the host immunity. Typically, the majority of primary EBV infections are asymptomatic, which occurs during infancy and early childhood in areas where general hygiene conditions are less strictly enforced. […] EBV initiates a distinct dual-life cycle, either latent (nonproductive) infection or lytic (productive) replication. […] The B-lymphotropic nature of EBV is evidenced by the potent transforming ability of the virus to immortalize normal resting B lymphocytes in vitro, converting them into permanently growing lymphoblastoid cell lines (LCLs). […] EBV remains the most efficient transforming agent, which rapidly immortalizes B cells during in vitro infection. […] The expression of EBERs, as well as miRNAs, is present in all forms of latency. […] Understanding the relationship between the EBV virus with its host cell and the interaction between EBV latent with lytic antigens in the context of associated cancers will continue to be an important topic for future studies.

• #1 A Review of Epstein Barr Virus Immunity, Pathogenesis and Immunotherapies

  https://digitalcommons.uri.edu/srhonorsprog/608/

  Epstein Barr Virus (EBV), a member of the Herpesviridae family, is commonly known as the cause of infectious mononucleosis. […] EBV first establishes infection in epithelial cells of the oropharynx, where it is lytic, and later establishes latent infection in B cells, where it exists in latency for remainder of the hosts lifetime. […] Through mechanisms involving EBV lytic proteins, BGLF5, BNLF2, gp42, BILF1, BZLF1, EBV evades the initial immune response and adapts a latency program where EBNA1 and microRNAs enable the virus to further evade host immune mechanisms throughout all latency stages. […] During the latent stage, EBV acts on cell proliferative and cancer protecting mechanisms to cause cancers of epithelial and lymphatic origins. […] EBVs major oncogene, LMP1, induces signaling pathways involving NF-B and PI3K to cause cellular proliferation and survival.

• #1 The contribution of ebv to the pathogenesis of classical hodgkin lymphoma – Vrzalikova – Annals of Lymphoma

  https://aol.amegroups.org/article/view/7322/html

  EBV-infected HRS cells express a restricted pattern of virus latency characterised by the presence of EBVs maintenance protein, EBNA1, as well as both latent membrane proteins. […] A subset of viral miRNA are also expressed. […] While the contribution of the EBV latent proteins to the pathogenesis of cHL is increasingly better understood, the roles of the EBV miRNAs have only just begun to be explored. […] EBNA1 is essential for the maintenance of EBV episomes in infected cells, as it is a key viral replication factor and is responsible for tethering viral genomes to the chromosomes of the host cell; loss of EBNA1 expression therefore results in the loss of EBV genomes during cell division. […] EBNA1 is also a transcription factor that can bind to viral and cellular promoters. […] EBNA1 inhibits TGF signalling, in part by modulating the levels of SMAD2. […] EBNA1 also decreases expression of the TGF target gene, PTPRK, which in turn promotes the growth and survival of HRS cells.

• #1 A yeast model for the mechanism of the Epstein-Barr virus immune evasion identifies a new therapeutic target to interfere with the virus stealthiness

  https://microbialcell.com/researcharticles/a-yeast-model-for-the-mechanism-of-the-epstein-barr-virus-immune-evasion-identifies-a-new-therapeutic-target-to-interfere-with-the-virus-stealthiness/

  The central glycine-alanine repeat (GAr) of EBNA1 plays a critical role in this immune evasion strategy as it inhibits the translation of its own mRNA in cis, thereby limiting the production of EBNA1-derived antigenic peptides. […] GAr-based EBNA1 immune evasion has been considered a relevant therapeutic target to treat EBV-related cancers, hence there is a need to develop cell-based assays that allow high throughput screenings. […] Hence, based on these yeast results, the role of NCL in EBNA1 immune evasion was deciphered in EBV-infected human cells, leading to the formal demonstration that human NCL is involved in GAr-based limitation of translation and antigen presentation. […] Importantly, this interaction is druggable since the G4 ligand PhenDC3 prevents NCL from binding to G4 formed in the GAr mRNA sequence of EBNA1 mRNA and stimulates GAr-limited translation and antigen presentation.

• #1 The contribution of ebv to the pathogenesis of classical hodgkin lymphoma – Vrzalikova – Annals of Lymphoma

  https://aol.amegroups.org/article/view/7322/html

  EBV also influences host miRNA expression in cHL. […] For example, Navarro et al. observed a subset of 10 host miRNAs whose expression was influenced by the presence of EBV. […] Among these, miR-96, miR-128a, miR-128b were selectively down regulated in EBV-positive cHL. […] The authors also reported a distinctive signature of 25 miRNAs that were differentially expressed between cHL and reactive lymph nodes. […] The TME is a defining feature of cHL and there is some evidence that EBV is at least partly responsible for reshaping this TME through expression of the latent genes, and also potentially through limited induction of the lytic cycle. […] For example, LMP1 an increase production of a diverse array of different chemokines and cytokines. […] EBNA1 can also influence the transcription of genes encoding key soluble factors, for example the chemokine CCL20 which is important in the chemo-attraction of regulatory T cells.

• #1 The contribution of ebv to the pathogenesis of classical hodgkin lymphoma – Vrzalikova – Annals of Lymphoma

  https://aol.amegroups.org/article/view/7322/html

  LMP1 is a constitutively active homologue of CD40 that has been shown to activate NF-B, JAK/STAT, AP-1 and phosphatidylinositol-3 kinase (PI3K)/AKT signalling. […] While LMP1 might be responsible for activating these pathways in EBV-positive cHL, mutations in components of these signalling pathways appear to be necessary when the virus is absent. […] The requirement for more genetic changes in EBV-negative cHL is supported by other studies which show that EBV-positive cHL has significantly fewer chromosome abnormalities than EBV-negative cHL. […] EBV appears to be crucial for the survival of HRS progenitors harbouring so called crippling mutations in immunoglobulin genes; these mutations are found almost exclusively in EBV positive cases. […] EBV efficiently immortalises BCR-negative GC B cells in vitro; an effect that is dependent upon LMP2A which provides a BCR-like signalling function. […] LMP2A also contributes to the transcriptional programme of cHL, for example by reducing the expression of numerous B cell transcription factors, including EBF1 and E2A.

• #1 A Review of Epstein Barr Virus Immunity, Pathogenesis and Immunotherapies

  https://digitalcommons.uri.edu/srhonorsprog/608/

  EBVs nuclear antigen, EBNA1, which is present in all latency stages, is able to induce anti-apoptotic effects through inhibition of p53. […] EBNA2, the EBNA3 family, LMP2, EBERs, and microRNAs also aid in cellular proliferation, survival, and migration through mechanisms involving PI3K, PKR, and induction of cellular gene expression. […] Although there is currently no vaccine to prevent EBV from establishing chronic infection, these therapies show potential to treat its pathogenic sequelae.

• #1 Infectious Mononucleosis – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/herpesviruses/infectious-mononucleosis

  After exposure in the oral cavity, EBV infects B lymphocytes. Morphologically abnormal (atypical) lymphocytes develop, mainly from CD8+ T cells that respond to the infection. […] After primary infection, EBV remains within the host, primarily in B lymphocytes, for life and undergoes intermittent asymptomatic shedding from the oropharynx. The virus is detectable in oropharyngeal secretions of 10 to 20% of healthy EBV-seropositive adults. […] Shedding increases in frequency and titer in patients who are immunocompromised (eg, organ allograft recipients, people living with HIV). […] EBV is statistically associated with and likely has a causal role in Burkitt lymphoma, certain B-cell tumors in patients who are immunocompromised, certain forms of Hodgkin lymphoma, nasopharyngeal carcinoma, certain gastric cancers, and multiple sclerosis. […] EBV does not cause chronic fatigue syndrome. However, it rarely causes a syndrome that may include fever, interstitial pneumonitis, pancytopenia, hepatitis, or uveitis (ie, chronic active EBV).

• #1 Epstein–Barr virus and multiple sclerosis | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-022-00770-5

  EpsteinBarr virus (EBV) is a ubiquitous human lymphotropic herpesvirus with a well-established causal role in several cancers. […] Recent studies have provided compelling epidemiological and mechanistic evidence for a causal role of EBV in multiple sclerosis (MS). […] How a ubiquitous virus that typically leads to benign latent infections can promote cancer and autoimmune disease in at-risk populations is not fully understood. […] We focus on EBV contributing to MS through reprogramming of latently infected B lymphocytes and the chronic presentation of viral antigens as a potential source of autoreactivity through molecular mimicry. […] We consider how knowledge of EBV-associated cancers may be instructive for understanding the role of EBV in MS and discuss the potential for therapies that target EBV to treat MS.

• #1 Study identifies how Epstein-Barr virus triggers multiple sclerosis | News Center

  https://med.stanford.edu/news/all-news/2022/01/epstein-barr-virus-multiple-sclerosis.html

  A new study found that part of the Epstein-Barr virus mimics a protein made in the brain and spinal cord, leading the immune system to mistakenly attack the body’s nerve cells. […] Now, a study led by Stanford Medicine researchers has proved that the Epstein-Barr virus, a common type of herpes virus, triggers multiple sclerosis by priming the immune system to attack the body’s own nervous system. […] This means that when the immune system attacks EBV to clear the virus, it also ends up targeting GlialCAM in the myelin. […] This is the first time anyone has shown rather definitively that a virus is the trigger for multiple sclerosis. […] EBV tricks the immune system into responding not only to the virus, but also to this critical component of the cells that make up the white matter in our brains.

• #1 How Epstein-Barr Virus May Trigger MS | National MS SocietyNational Multiple Sclerosis Society LogoNational Multiple Sclerosis Society LogoOpen search

  https://www.nationalmssociety.org/news-and-magazine/news/potential-mechanism-epstein-barr-virus

  Investigators at Stanford University and their collaborators have identified a mechanism for how the Epstein-Barr virus (EBV), a known risk factor for multiple sclerosis, may prompt the immune system to attack brain cells to trigger MS. […] This suggests that the molecule on brain cells mimics the structure of the EBV component and can set off an autoimmune process. […] This “cross-reactivity” means that when the immune system is doing its job to try to fight EBV, it may also attack myelin-making cells. […] This study suggests that any EBV vaccine to be developed should not include the particular EBV component (EBNA1) that might cross-react and cause an autoimmune reaction to myelin-making cells.

• #1 Discovered a new mechanism against Epstein-Barr virus infection – El·lipse

  https://ellipse.prbb.org/discovered-a-new-mechanism-against-epstein-barr-virus-infection/

  A study in which UPF and IMIM have collaborated has discovered how Natural Killer cells of the immune system would reduce the mononucleosis virus infections. […] Researchers from the Department of Experimental and Health Sciences, Pompeu Fabra University (DCEXS-UPF) and the Hospital del Mar Medical Research Institute (IMIM) have found the way that the Natural Killer (NK) cells of the immune system reduce Epstein-Barr virus infections without killing B lymphocytes, their host cells. […] Now, a scientific team discovered that when NKs are activated by the presence of antibodies against viral particles before the virus enters the body, they could recognize and eliminate these viral particles without killing the lymphocytes. […] According to the authors, the mechanism could also be applied to other viruses infections, but its effectiveness is yet to be verified and further research will be needed.

• #1 A New Mechanism To Inhibit Epstein-Barr Virus Infection; The Virus Responsible For Kissing Disease And Several Types Of Cancer | Molecular Genetics

  https://moleculargenetics.utoronto.ca/news/new-mechanism-inhibit-epstein-barr-virus-infection-virus-responsible-kissing-disease-and

  Most people are infected with Epstein-Barr virus (EBV); a herpesvirus that establishes a lifetime infection with no current treatments or vaccines. […] A proteomics experiment in Dr. Lori Frappiers lab identified an interaction between an EBV protein (BORF2) and a cellular DNA mutating enzyme called APOBEC3B. […] They further showed that BORF2 was necessary to protect EBV genomes from mutation by APOBEC3B, which impairs the infectivity of the virus. […] This provides a new opportunity to inhibit EBV infection by interfering with the BORF2-APOBEC3B interaction.

• #1 Epstein-Barr virus-associated lymphomas: Sapienza scientists identify a new mechanism by which infected tumour cells deceive the immune system  | Sapienza Università di Roma

  https://www.uniroma1.it/en/notizia/epstein-barr-virus-associated-lymphomas-sapienza-scientists-identify-new-mechanism-which

  A new study coordinated by Sapienza University of Rome has clarified for the first time how this virus uses one of its proteins to compromise the immune response of tumour cells. […] One of the most promising therapeutic strategies for the treatment of virus-associated tumours is immunotherapy and only a more in-depth understanding of the molecular mechanisms involved will allow its extended therapeutic use. […] The viral protein EBNA2, encoded by the Epstein-Barr virus, reduces the expression of the ICOSL protein, a crucial molecule both for the recognition of the tumour cell by the immune system and for the generation of efficient antiviral antibodies. […] EBV uses the viral protein EBNA2 to increase the expression of PD-L1 on the surface of the tumour cell. Through this mechanism, EBV prevents the immune system from acting against the tumour.

• #1 Infectious Mononucleosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2023/0100/infectious-mononucleosis.html

  Infectious mononucleosis is a viral syndrome characterized by fever, pharyngitis, and posterior cervical lymphadenopathy. It is usually caused by Epstein-Barr virus and most often affects adolescents and young adults 15 to 24 years of age. Primary transmission is through close personal contact with a person who is infected, particularly their saliva. […] Epstein-Barr virus infection has been linked to nine types of cancer, including Hodgkin lymphoma, non-Hodgkin lymphoma, and nasopharyngeal carcinoma, and some autoimmune diseases. […] The presence of elevated liver enzymes increases clinical suspicion for infectious mononucleosis in the setting of a negative heterophile antibody test result. […] Individuals with infectious mononucleosis should not participate in athletic activity for three weeks following symptom onset to reduce the risk of splenic rupture, beginning with light, noncontact exercise.

• #1 Infectious Mononucleosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2023/0100/infectious-mononucleosis.html

  Hospitalized patients with infectious mononucleosis have been shown to have increased hepatic transaminase levels. […] EBV infection can lead to severe and potentially fatal complications in patients with immunodeficiency, including X-linked lymphoproliferative disease. […] EBV has been linked to two pre-malignant lymphoproliferative diseases and nine types of cancer. […] Evidence suggests that prior EBV infection increases the risk of autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis.

• #1 Mononucleosis – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/mononucleosis/symptoms-causes/syc-20350328

  Infectious mononucleosis (mono) is often called the kissing disease. The virus that causes mono (Epstein-Barr virus) is spread through saliva. […] The most common cause of mononucleosis is the Epstein-Barr virus, but other viruses also can cause similar symptoms. […] Mononucleosis may cause enlargement of the spleen. In extreme cases, your spleen may rupture, causing sharp, sudden pain in the left side of your upper abdomen. […] The Epstein-Barr virus can cause much more serious illness in people who have impaired immune systems.

• #1 Wistar Scientists Make Pivotal Discovery on the Mechanism of Epstein-Barr Virus Latent Infection – The Wistar Institute

  https://www.wistar.org/press-releases/wistar-scientists-make-pivotal-discovery-on-the-mechanism-of-epstein-barr-virus-latent-infection/

  EBV establishes life-long, latent infection in B lymphocytes, which can contribute to development of different cancer types, including Burkitts lymphoma, nasopharyngeal carcinoma (NPC) and Hodgkins lymphoma. […] While it was known that EBNA1 mediates replication and partitioning of the episome during division of the host cell, the exact mechanism was not clear. The new study sheds light on the process and describes how the newly discovered enzymatic activity of EBNA1 is required to complete replication of the viral genome and maintenance of the episomal form. […] Our findings suggest that one could create small molecules to trap the protein bound to DNA and potentially block replication termination and episome maintenance, similar to known inhibitors of topoisomerases, said Jayaraju Dheekollu, Ph.D., first author on the study and staff scientist in the Lieberman Lab. Such inhibitors may be used to inhibit EBV-induced transformation and treat EBV-associated malignancies.

• #1 Epstein–Barr Virus History and Pathogenesis

  https://www.mdpi.com/1999-4915/15/3/714

  Epstein–Barr virus (EBV) is the first identified human oncogenic virus that can establish asymptomatic life-long persistence. […] Although EBV molecular biology and EBV-related diseases have been continuously investigated for nearly 60 years, the mechanism of viral-mediated transformation, as well as the precise role of EBV in promoting these diseases, remain a major challenge yet to be completely explored. […] It is estimated that more than 250,000 cases of cancer every year are induced by EBV, and that approximately 2% of all cancer deaths are due to EBV-attributed malignancies. Improved understanding of pathogenic mechanisms, which drives the many aforementioned diseases, provides clues as to potential opportunities for recognizing and identifying early and effective treatments at different stages in the development of EBV-associated diseases.

• #2 Epstein–Barr Virus History and Pathogenesis

  https://www.mdpi.com/1999-4915/15/3/714

  Epstein–Barr virus (EBV) is the first identified human oncogenic virus that can establish asymptomatic life-long persistence. […] Although EBV molecular biology and EBV-related diseases have been continuously investigated for nearly 60 years, the mechanism of viral-mediated transformation, as well as the precise role of EBV in promoting these diseases, remain a major challenge yet to be completely explored. […] It is estimated that more than 250,000 cases of cancer every year are induced by EBV, and that approximately 2% of all cancer deaths are due to EBV-attributed malignancies. Improved understanding of pathogenic mechanisms, which drives the many aforementioned diseases, provides clues as to potential opportunities for recognizing and identifying early and effective treatments at different stages in the development of EBV-associated diseases.

• #2 Epstein-Barr Virus (EBV) Infectious Mononucleosis (Mono): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/784513-overview

  Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that causes lifelong infections in humans. It is primarily spread through intimate contact with oropharyngeal secretions, though it can also be transmitted via genital secretions, blood transfusions, and organ transplants. Upon initial infection, EBV specifically targets B lymphocytes in the oropharyngeal epithelium. Following this acute phase, the virus can persist in oropharyngeal secretions for up to 32 weeks and remain in the body for decades. […] Once EBV infects B lymphocytes, atypical lymphocytes develop, primarily from CD8+ T cells that respond to the viral infection. After the primary infection, EBV remains dormant in the host, mainly within B lymphocytes, and undergoes intermittent asymptomatic shedding from the oropharynx. In healthy adults who are EBV-seropositive, the virus can be detected in the oropharyngeal secretions of 10-20% of individuals. This shedding is more frequent and at higher levels in immunocompromised patients, such as organ transplant recipients and individuals living with HIV.

• #2 Infectious Mononucleosis (EBV)

  https://www.atsu.edu/faculty/chamberlain/website/lectures/lecture/mono.htm

  Epithelial cells of the oropharynx are the portals of EBV infection. The virus is transmitted primarily by repeated contact with oropharyngeal secretions, and is primarily transmitted by adults 30-50 days or by children 10-14 days following infection. It can be isolated from saliva, blood, and lymphatics. EBV invades B lymphocytes by means of their CD21 receptors; within 18-24 hours, EBV antigens are detectable within the lymphocyte nucleus. […] The signs and symptoms of infectious mononucleosis are the result of viral replication and the host immune response to viral antigens. Infected B lymphocytes spread the infection throughout the reticuloendothelial system (e.g., liver, spleen, and peripheral lymph nodes). EBV infection of B lymphocytes results in a humoral and cellular response to the virus. EBV initiates B lymphocyte proliferation (plasma cells) and immortalization (memory B lymphocyte) without the role of T-helper cells. EBV is a B-cell mitogen that can cause many B lymphocytes to become antibody-producing plasma cells.

• #2 Mechanism of EBV to Invade Host Cells – Creative Diagnostics

  https://www.creative-diagnostics.com/blog/index.php/mechanism-of-ebv-to-invade-host-cells/

  EBV is a virus transmitted through saliva. Oral mucosal epithelial cells are the first threshold for their invasive host cells. EBVs primary infection is considered to be caused by viruses through the oropharyngeal epithelium. Infection of naive B cells present in Waldeyers ring of tonsils. EBV shows obvious tendency to B lymphocytes, which is easy to infect B cells and convert initial B cells into proliferative lymphocytes. Viral glycoproteins including gp350, gHgL, gB and gp42 mediate the preferential binding of EBV to B cells by interacting with the complement receptor CR2 (CD21) on the surface of B cells, and then the envelope glycoprotein gp42 and gp85/gp25 form a fusion protein triple molecule Complex. The GP42 in the complex is combined with the HLA II molecular molecules, and caused the virus cell fusion under the participation of GP85/GP25 and GP110 glycoprotein.

• #2 Epstein–Barr virus – Wikipedia

  https://en.wikipedia.org/wiki/Epstein%E2%80%93Barr_virus

  The EpsteinBarr virus (EBV) is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus and is also called human herpesvirus 4 (HHV-4). EpsteinBarr virus (EBV) is the first identified oncogenic virus, or a virus that can cause cancer. EBV establishes permanent infection in humans. It causes infectious mononucleosis and is also tightly linked to many malignant diseases (cancers). […] EBV infects B cells of the immune system and epithelial cells. Once EBV’s initial lytic infection is brought under control, EBV latency persists in the individual’s memory B cells for the rest of their life. […] EBV infection of B lymphocytes leads to „immortalization” of these cells, meaning that the virus causes them to continue dividing indefinitely. Normally, cells have a limited lifespan and eventually die, but when EBV infects B lymphocytes, it alters their behavior, making them „immortal” in the sense that they can keep dividing and surviving much longer than usual. This allows the virus to persist in the body for the individual’s lifetime.

• #2 Infectious mononucleosis – Wikipedia

  https://en.wikipedia.org/wiki/Infectious_mononucleosis

  The virus replicates first within epithelial cells in the pharynx (which causes pharyngitis, or sore throat), and later primarily within B cells (which are invaded via their CD21). The host immune response involves cytotoxic (CD8-positive) T cells against infected B lymphocytes, resulting in enlarged, reactive lymphocytes (Downey cells). […] When the infection is acute (recent onset, instead of chronic), heterophile antibodies are produced. […] Mononucleosis is sometimes accompanied by secondary cold agglutinin disease, an autoimmune disease in which abnormal circulating antibodies directed against red blood cells can lead to a form of autoimmune hemolytic anemia. The cold agglutinin detected is of anti-i specificity.

• #2 Pathogenesis, diagnostic testing, and management of mononucleosis: because Epstein-Barr virus is highly contagious and linked to various complications and malignancies, familiarity with transmission risks and the differential diagnosis is essential – Docu

  https://go.gale.com/ps/i.do?id=GALE%7CA301182056&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=15471896&p=AONE&sw=w

  Infectious mononucleosis (IM), formerly known as glandular fever, is a common clinical syndrome associated with Epstein-Barr virus (EBV). […] Epstein-Barr virus is a herpesvirus that primarily infects the epithelial cells of the oropharynx and tonsils. Infection in the tonsillar crypt epithelial cells results in viral replication and shedding. […] EBV infects B lymphocytes, resulting in the proliferation and secretion of a number of different types of antibodies, including EBV-specific antibodies; heterophile antibodies; and autoantibodies, such as rheumatoid factor and antinuclear antibodies. The secretion of these various antibodies is referred to as polyclonal activity. […] The symptoms of acute IM are a direct result of cytokines that are released from activated T cells. Because the symptoms of EBV infection are T-cell mediated, the initial viral load will determine the level of T-cell response and, thus, the severity of illness. Increased viral load will lead to increased T-cell response and increased symptoms. EBV can remain latent in infected B lymphocytes, which serve as lifelong viral reservoirs, expressing only a restricted number of EBV genes that are hidden from host immune surveillance cells. If the virus is reactivated, shedding can occur in the saliva and genital secretions of asymptomatic persons.

• #2 Epstein-Barr virus infection: the micro and macro worlds | Virology Journal | Full Text

  https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02187-9

  EBV infection is divided into three main phases: primary infection and lytic replication, latency and lytic reactivation. […] After primary infection, the virus remains dormant, with memory B cells serving as the main reservoir of their persistence. […] EBV can maintain in the latent infection phase in the human host, which is an important reason why the virus cannot be eradicated and can maintain lifelong persistence. […] During the latent infection phase, EBV expresses only a limited subset of viral genes and noncoding RNAs, including six nuclear antigens, EBNA-1, EBNA-2, EBNA-3 A, EBNA-3B, EBNA-3 C, and LP; three latent membrane proteins (LMPs), LMP-1 and LMP-2 A/B; and two types of non-coding RNA that are not translated into proteins, EBV-encoded RNAs (EBERs) and microRNAs (miRNAs).

• #2 A Review of Epstein Barr Virus Immunity, Pathogenesis and Immunotherapies

  https://digitalcommons.uri.edu/srhonorsprog/608/

  Epstein Barr Virus (EBV), a member of the Herpesviridae family, is commonly known as the cause of infectious mononucleosis. […] EBV first establishes infection in epithelial cells of the oropharynx, where it is lytic, and later establishes latent infection in B cells, where it exists in latency for remainder of the hosts lifetime. […] Through mechanisms involving EBV lytic proteins, BGLF5, BNLF2, gp42, BILF1, BZLF1, EBV evades the initial immune response and adapts a latency program where EBNA1 and microRNAs enable the virus to further evade host immune mechanisms throughout all latency stages. […] During the latent stage, EBV acts on cell proliferative and cancer protecting mechanisms to cause cancers of epithelial and lymphatic origins. […] EBVs major oncogene, LMP1, induces signaling pathways involving NF-B and PI3K to cause cellular proliferation and survival.

• #2 Infectious Mononucleosis – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/herpesviruses/infectious-mononucleosis

  After exposure in the oral cavity, EBV infects B lymphocytes. Morphologically abnormal (atypical) lymphocytes develop, mainly from CD8+ T cells that respond to the infection. […] After primary infection, EBV remains within the host, primarily in B lymphocytes, for life and undergoes intermittent asymptomatic shedding from the oropharynx. The virus is detectable in oropharyngeal secretions of 10 to 20% of healthy EBV-seropositive adults. […] Shedding increases in frequency and titer in patients who are immunocompromised (eg, organ allograft recipients, people living with HIV). […] EBV is statistically associated with and likely has a causal role in Burkitt lymphoma, certain B-cell tumors in patients who are immunocompromised, certain forms of Hodgkin lymphoma, nasopharyngeal carcinoma, certain gastric cancers, and multiple sclerosis. […] EBV does not cause chronic fatigue syndrome. However, it rarely causes a syndrome that may include fever, interstitial pneumonitis, pancytopenia, hepatitis, or uveitis (ie, chronic active EBV).

• #2 Epstein-Barr Virus: Molecular Mechanism of Lymphoma Development Elucidated | German Center for Infection Research

  https://www.dzif.de/en/epstein-barr-virus-molecular-mechanism-lymphoma-development-elucidated

  Epstein-Barr Virus (EBV) is widespread and very contagious: according to the World Health Association, more than 90 percent of the global population are infected with this virus throughout their lives. The virus causes B and T cell lymphomas (cancer of the lymphatic system) as well as carcinomas (epithelial cell cancer) in humans. […] An oncogene is a gene that has the potential to cause cancer. Latent membrane protein 1 (LMP1) is the primary oncogene of EBV: It drives oncogenic cell transformation and tumour development. The authors show in the study that the viral LMP1 protein forms a direct complex with TRAF6, a protein derived from the host cell that is involved in biochemical signal transmission processes such as the activation of the NF-kappaB pathway (a cellular pathway, regulating genes involved in immunity, inflammation and cell survival). Furthermore, the researchers provide detailed insights into the molecular functions and structure of the LMP1-TRAF6 complex and demonstrate that the direct interaction of the two proteins is critical for LMP1 to activate the NF-kappaB pathway and to promote cell survival in lymphoma cells.

• #2 A Mechanism by Which Epstein-Barr Virus Could Increase Risk for Multiple Sclerosislogo-32logo-40logo-60NEJM Journal WatchnejmJW_1L_RGB-b

  https://www.jwatch.org/na54843/2022/04/12/mechanism-which-epstein-barr-virus-could-increase-risk

  Molecular mimicry between an EBV protein and a molecule expressed in MS plaques might cause autoimmunity. […] Recently, a large epidemiologic study identified Epstein-Barr virus (EBV) infection as one likely contributing factor in multiple sclerosis (MS): New EBV infection increased relative risk for developing MS by 32-fold in healthy young adults (NEJM JW Gen Med Mar 1 2022 and Science 2022; 375:296). […] In a study from Stanford, researchers show that the structure of one part of a critical EBV protein, EBV nuclear antigen 1 (EBNA1), is very similar to GlialCAM, a molecule that is prominent in astrocytes and oligodendrocytes (myelin-generating cells) and that is expressed heavily in MS plaques. […] Antibodies against EBNA1 also bind tightly to GlialCAM — an example of molecular mimicry.

• #2 Epstein-Barr virus-associated lymphomas: Sapienza scientists identify a new mechanism by which infected tumour cells deceive the immune system  | Sapienza Università di Roma

  https://www.uniroma1.it/en/notizia/epstein-barr-virus-associated-lymphomas-sapienza-scientists-identify-new-mechanism-which

  This new study reveals a further and fundamental mechanism that deceives the immune system and promotes tumour proliferation. […] We have now identified EBNA2, a viral protein as the main negative regulator of ICOSL. It does so by increasing microRNA-24. This is how the virus, and together with it, also the tumour cell, escape from immune control. […] By inhibiting the activity of miR-24 scientists can reestablish ICOSL expression on the tumor cell and make it again visible to the immune system. […] For the first time we have clarified in the field of virology how the Epstein-Barr virus uses one of its most important proteins to compromise immune responses.

• #2 Infectious Mononucleosis: Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2023/0100/infectious-mononucleosis.html

  Infectious mononucleosis is a viral syndrome characterized by fever, pharyngitis, and posterior cervical lymphadenopathy. It is usually caused by Epstein-Barr virus and most often affects adolescents and young adults 15 to 24 years of age. Primary transmission is through close personal contact with a person who is infected, particularly their saliva. […] Epstein-Barr virus infection has been linked to nine types of cancer, including Hodgkin lymphoma, non-Hodgkin lymphoma, and nasopharyngeal carcinoma, and some autoimmune diseases. […] The presence of elevated liver enzymes increases clinical suspicion for infectious mononucleosis in the setting of a negative heterophile antibody test result. […] Individuals with infectious mononucleosis should not participate in athletic activity for three weeks following symptom onset to reduce the risk of splenic rupture, beginning with light, noncontact exercise.

• #2 About Epstein-Barr Virus (EBV) | EBV and Mono | CDC

  https://www.cdc.gov/epstein-barr/about/index.html

  EBV is the most common cause of infectious mononucleosis, also called „mono.” […] After you get an EBV infection, the virus becomes latent (inactive) in your body. In some cases, the virus may reactivate. […] If it reactivates, you can potentially infect others no matter how much time has passed since the first infection. […] Most people get better in 2 to 4 weeks. There is no specific treatment for EBV.

• #2 The contribution of ebv to the pathogenesis of classical hodgkin lymphoma – Vrzalikova – Annals of Lymphoma

  https://aol.amegroups.org/article/view/7322/html

  A subset of cHL patients harbor EBV in their tumour cells. […] Although the contribution of EBV to the pathogenesis of cHL has been debated, we argue that differences in the epidemiology, genetics, and biology of EBV-positive compared with EBV-negative cHL strongly suggest a key role for the virus. […] Notwithstanding debate over EBVs exact contribution to the oncogenic process in cHL, there is undoubtedly an opportunity to exploit the presence of EBV in tumours for patient benefit.

• #3 Epstein–Barr virus – Wikipedia

  https://en.wikipedia.org/wiki/Epstein%E2%80%93Barr_virus

  The EpsteinBarr virus (EBV) is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus and is also called human herpesvirus 4 (HHV-4). EpsteinBarr virus (EBV) is the first identified oncogenic virus, or a virus that can cause cancer. EBV establishes permanent infection in humans. It causes infectious mononucleosis and is also tightly linked to many malignant diseases (cancers). […] EBV infects B cells of the immune system and epithelial cells. Once EBV’s initial lytic infection is brought under control, EBV latency persists in the individual’s memory B cells for the rest of their life. […] EBV infection of B lymphocytes leads to „immortalization” of these cells, meaning that the virus causes them to continue dividing indefinitely. Normally, cells have a limited lifespan and eventually die, but when EBV infects B lymphocytes, it alters their behavior, making them „immortal” in the sense that they can keep dividing and surviving much longer than usual. This allows the virus to persist in the body for the individual’s lifetime.

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