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The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...
es in humans. EBV is a
double-stranded DNA virus A DNA virus is a virus that has a genome made of deoxyribonucleic acid (DNA) that is replicated by a DNA polymerase. They can be divided between those that have two strands of DNA in their genome, called double-stranded DNA (dsDNA) viruses, and ...
. It is best known as the cause of
infectious mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adult ...
("mono" or "glandular fever"). It is also associated with various non-malignant,
premalignant A precancerous condition is a condition, tumor or lesion involving abnormal cells which are associated with an increased risk of developing into cancer. Clinically, precancerous conditions encompass a variety of abnormal tissues with an increased ...
, and malignant Epstein–Barr virus-associated lymphoproliferative diseases such as Burkitt lymphoma,
hemophagocytic lymphohistiocytosis Hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis (British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a ...
, and
Hodgkin's lymphoma Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition w ...
; non-lymphoid malignancies such as gastric cancer and nasopharyngeal carcinoma; and conditions associated with
human immunodeficiency virus The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immun ...
such as hairy leukoplakia and
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enla ...
s. The virus is also associated with the childhood disorders of
Alice in Wonderland syndrome Alice in Wonderland syndrome (AIWS), also known as Todd's syndrome or dysmetropsia, is a neuropsychological condition that causes a distortion of perception. People may experience distortions in visual perception of objects, such as appearing sma ...
and acute cerebellar ataxia and, by some evidence, higher risks of developing certain autoimmune diseases, especially
dermatomyositis Dermatomyositis (DM) is a long-term inflammatory disorder which affects skin and the muscles. Its symptoms are generally a skin rash and worsening muscle weakness over time. These may occur suddenly or develop over months. Other symptoms may inc ...
, systemic lupus erythematosus,
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...
, and Sjögren's syndrome. About 200,000 cancer cases globally per year are thought to be attributable to EBV. In 2022, a large study (population of 10 million over 20 years) suggested EBV as the leading cause of multiple sclerosis, with a recent EBV infection causing a 32-fold increase in the risk of developing multiple sclerosis. Related non-technical article: Infection with EBV occurs by the oral transfer of saliva and genital secretions. Most people become infected with EBV and gain
adaptive immunity The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
. In the United States, about half of all five-year-old children and about 90% of adults have evidence of previous infection. Infants become susceptible to EBV as soon as maternal antibody protection disappears. Many children become infected with EBV, and these infections usually cause no symptoms or are indistinguishable from the other mild, brief illnesses of childhood. In the United States and other developed countries, many people are not infected with EBV in their childhood years. When infection with EBV occurs during adolescence or young adulthood, it causes
infectious mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adult ...
35 to 50% of the time. EBV infects B cells of the immune system and
epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
. Once EBV's initial
lytic The lytic cycle ( ) is one of the two cycles of viral reproduction (referring to bacterial viruses or bacteriophages), the other being the lysogenic cycle. The lytic cycle results in the destruction of the infected cell and its membrane. Bacter ...
infection is brought under control, EBV latency persists in the individual's
memory B cell In immunology, a memory B cell (MBC) is a type of B lymphocyte that forms part of the adaptive immune system. These cells develop within germinal centers of the secondary lymphoid organs. Memory B cells circulate in the blood stream in a quiesc ...
s for the rest of their life.


Virology


Structure and genome

The
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...
is about 122–180 nm in diameter and is composed of a double helix of deoxyribonucleic acid (DNA) which contains about 172,000 base pairs encoding 85
gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s. The DNA is surrounded by a protein nucleocapsid, which is surrounded by a tegument made of protein, which in turn is surrounded by an
envelope An envelope is a common packaging item, usually made of thin, flat material. It is designed to contain a flat object, such as a letter or card. Traditional envelopes are made from sheets of paper cut to one of three shapes: a rhombus, a sh ...
containing both
lipids Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
and surface projections of
glycoproteins Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosy ...
, which are essential to infection of the host cell. In July 2020, a team of researchers reported the first complete atomic model of the nucleocapsid of the virus. This "first complete atomic model ncludesthe icosahedral capsid, the capsid-associated tegument complex (CATC) and the dodecameric portal--the viral genome translocation apparatus."


Tropism

The term viral tropism refers to which cell types that EBV infects. EBV can infect different cell types, including
B cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...
and
epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
. The viral three-part glycoprotein complexes of gHgL gp42 mediate B cell membrane fusion; although the two-part complexes of gHgL mediate epithelial cell membrane fusion. EBV that are made in the B cells have low numbers of gHgLgp42 complexes, because these three-part complexes interact with Human-leukocyte-antigen class II molecules present in B cells in the endoplasmic reticulum and are degraded. In contrast, EBV from epithelial cells are rich in the three-part complexes because these cells do not normally contain HLA class II molecules. As a consequence, EBV made from B cells are more infectious to epithelial cells, and EBV made from epithelial cells are more infectious to B cells. Viruses lacking the gp42 portion are able to bind to human B cells, but unable to infect.


Replication cycle


Entry to the cell

EBV can infect both B cells and epithelial cells. The mechanisms for entering these two cells are different. To enter B cells, viral glycoprotein gp350 binds to cellular receptor
CD21 Complement receptor type 2 (CR2), also known as complement C3d receptor, Epstein-Barr virus receptor, and CD21 (cluster of differentiation 21), is a protein that in humans is encoded by the CR2 gene. CR2 is involved in the complement system. It ...
(also known as CR2). Then, viral glycoprotein gp42 interacts with cellular
MHC class II MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial ce ...
molecules. This triggers
fusion Fusion, or synthesis, is the process of combining two or more distinct entities into a new whole. Fusion may also refer to: Science and technology Physics *Nuclear fusion, multiple atomic nuclei combining to form one or more different atomic nucl ...
of the viral envelope with the cell membrane, allowing EBV to enter the B cell. Human CD35, also known as
complement receptor 1 Complement receptor type 1 (CR1) also known as C3b/C4b receptor or CD35 (cluster of differentiation 35) is a protein that in humans is encoded by the ''CR1'' gene. This gene is a member of the regulators of complement activation (RCA) family a ...
(CR1), is an additional attachment factor for gp350/220, and can provide a route for entry of EBV into CD21-negative cells, including immature B-cells. EBV infection downregulates expression of CD35. To enter epithelial cells, viral protein BMRF-2 interacts with cellular β1
integrins Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...
. Then, viral protein gH/gL interacts with cellular αvβ6/ αvβ8 integrins. This triggers
fusion Fusion, or synthesis, is the process of combining two or more distinct entities into a new whole. Fusion may also refer to: Science and technology Physics *Nuclear fusion, multiple atomic nuclei combining to form one or more different atomic nucl ...
of the viral envelope with the epithelial cell membrane, allowing EBV to enter the epithelial cell. Unlike B-cell entry, epithelial-cell entry is actually impeded by viral glycoprotein gp42. Once EBV enters the cell, the viral capsid dissolves and the viral genome is transported to the cell nucleus.


Lytic replication

The lytic cycle, or productive infection, results in the production of infectious virions. EBV can undergo lytic replication in both B cells and epithelial cells. In B cells, lytic replication normally only takes place after reactivation from latency. In epithelial cells, lytic replication often directly follows
viral entry Viral entry is the earliest stage of infection in the viral life cycle, as the virus comes into contact with the host cell and introduces viral material into the cell. The major steps involved in viral entry are shown below. Despite the variati ...
. For lytic replication to occur, the viral genome must be linear. The latent EBV genome is circular, so it must linearize in the process of lytic reactivation. During lytic replication, viral
DNA polymerase A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create ...
is responsible for copying the viral genome. This contrasts with latency, in which host-cell DNA polymerase copies the viral genome. Lytic gene products are produced in three consecutive stages: immediate-early, early, and late. Immediate-early lytic gene products act as transactivators, enhancing the
expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, o ...
of later lytic genes. Immediate-early lytic gene products include
BZLF1 ''BZLF1'' (BamHI Z fragment leftward open reading frame 1), also known as ''Zta'', ''EB1,'' is an immediate-early viral gene of the Epstein–Barr virus (EBV) of the Herpes Virus Family, which induces cancers and infects primarily the B-cells ...
(also known as Zta, EB1, associated with its product gene ''ZEBRA'') and BRLF1 (associated with its product gene ''Rta''). Early lytic gene products have many more functions, such as replication, metabolism, and blockade of
antigen processing Antigen processing, or the cytosolic pathway, is an immunological process that prepares antigens for presentation to special cells of the immune system called T lymphocytes. It is considered to be a stage of antigen presentation pathways. This pro ...
. Early lytic gene products include BNLF2. Finally, late lytic gene products tend to be proteins with structural roles, such as VCA, which forms the viral
capsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or ma ...
. Other late lytic gene products, such as BCRF1, help EBV evade the immune system. EGCG, a polyphenol in green tea, has shown in a study to inhibit EBV spontaneous lytic infection at the DNA, gene transcription, and protein levels in a time- and dose-dependent manner; the expression of EBV lytic genes'' Zta, Rta'', and early antigen complex EA-D (induced by ''Rta''), however, the highly stable '' EBNA-1'' gene found across all stages of EBV infection is unaffected. Specific inhibitors (to the pathways) suggest that Ras/MEK/MAPK pathway contributes to EBV lytic infection though BZLF1 and PI3-K pathway through BRLF1, the latter completely abrogating the ability of a BRLF1 adenovirus vector to induce the lytic form of EBV infection. Additionally, the activation of some genes but not others is being studied to determine just how to induce immune destruction of latently infected B-cells by use of either TPA or sodium butyrate.


Latency

Unlike lytic replication, latency does not result in production of virions. Instead, the EBV genome circular DNA resides in the cell nucleus as an
episome An episome is a special type of plasmid, which remains as a part of the eukaryotic genome without integration. Episomes manage this by replicating together with the rest of the genome and subsequently associating with metaphase chromosomes during m ...
and is copied by cellular
DNA polymerase A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create ...
. In latency, only a portion of EBV's genes are expressed. Latent EBV expresses its genes in one of three patterns, known as latency programs. EBV can latently persist within
B cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...
and
epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
, but different latency programs are possible in the two types of cell. EBV can exhibit one of three latency programs: Latency I, Latency II, or Latency III. Each latency program leads to the production of a limited, distinct set of viral proteins and viral
RNAs The Royal Naval Air Service (RNAS) was the air arm of the Royal Navy, under the direction of the Admiralty's Air Department, and existed formally from 1 July 1914 to 1 April 1918, when it was merged with the British Army's Royal Flying Corps t ...
. The nomenclature used here is that of Kieff. Other laboratories use different nomenclatures. Also, a program is postulated in which all viral protein expression is shut off (Latency 0). Within B cells, all three latency programs are possible. EBV latency within B cells usually progresses from Latency III to Latency II to Latency I. Each stage of latency uniquely influences B cell behavior. Upon infecting a resting naive B cell, EBV enters Latency III. The set of proteins and RNAs produced in Latency III transforms the B cell into a proliferating blast (also known as B cell activation). Later, the virus restricts its gene expression and enters Latency II. The more limited set of proteins and RNAs produced in Latency II induces the B cell to differentiate into a
memory B cell In immunology, a memory B cell (MBC) is a type of B lymphocyte that forms part of the adaptive immune system. These cells develop within germinal centers of the secondary lymphoid organs. Memory B cells circulate in the blood stream in a quiesc ...
. Finally, EBV restricts gene expression even further and enters Latency I. Expression of EBNA-1 allows the EBV genome to replicate when the memory B cell divides. Within epithelial cells, only Latency II is possible. In primary infection, EBV replicates in oropharyngeal epithelial cells and establishes Latency III, II, and I infections in B-lymphocytes. EBV latent infection of B-lymphocytes is necessary for virus persistence, subsequent replication in epithelial cells, and release of infectious virus into saliva. EBV Latency III and II infections of B-lymphocytes, Latency II infection of oral epithelial cells, and Latency II infection of NK- or T-cell can result in malignancies, marked by uniform EBV genome presence and gene expression.


Reactivation

Latent EBV in B cells can be reactivated to switch to lytic replication. This is known to happen ''in vivo'', but what triggers it is not known precisely. ''In vitro'', latent EBV in B cells can be reactivated by stimulating the B cell receptor, so it is likely reactivation ''in vivo'' takes place after latently infected B cells respond to unrelated infections.


Transformation of B-lymphocytes

When EBV infects B cells ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
'', lymphoblastoid cell lines eventually emerge that are capable of indefinite growth. The growth transformation of these cell lines is the consequence of viral protein expression. EBNA-2, EBNA-3C, and LMP-1 are essential for transformation, whereas EBNA-LP and the EBERs are not. Following natural infection with EBV, the virus is thought to execute some or all of its repertoire of gene expression programs to establish a persistent infection. Given the initial absence of host immunity, the lytic cycle produces large numbers of virions to infect other (presumably) B-lymphocytes within the host. The latent programs reprogram and subvert infected B-lymphocytes to proliferate and bring infected cells to the sites at which the virus presumably persists. Eventually, when host immunity develops, the virus persists by turning off most (or possibly all) of its genes, only occasionally reactivating to produce fresh virions. A balance is eventually struck between occasional viral reactivation and host immune surveillance removing cells that activate viral gene expression. The site of persistence of EBV may be bone marrow. EBV-positive patients who have had their own bone marrow replaced with bone marrow from an EBV-negative donor are found to be EBV-negative after transplantation.


Latent antigens

All EBV nuclear proteins are produced by alternative splicing of a transcript starting at either the Cp or Wp promoters at the left end of the
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
(in the conventional nomenclature). The genes are ordered ''EBNA-LP/EBNA-2/EBNA-3A/EBNA-3B/EBNA-3C/EBNA-1'' within the genome. The initiation codon of the EBNA-LP coding region is created by an alternate splice of the nuclear protein transcript. In the absence of this initiation codon,'' EBNA-2/EBNA-3A/EBNA-3B/EBNA-3C/EBNA-1'' will be expressed depending on which of these genes is alternatively spliced into the transcript.


Protein/genes


Subtypes of EBV

EBV can be divided into two major types, EBV type 1 and EBV type 2. These two subtypes have different EBNA-3 genes. As a result, the two subtypes differ in their transforming capabilities and reactivation ability. Type 1 is dominant throughout most of the world, but the two types are equally prevalent in
Africa Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...
. One can distinguish EBV type 1 from EBV type 2 by cutting the viral genome with a
restriction enzyme A restriction enzyme, restriction endonuclease, REase, ENase or'' restrictase '' is an enzyme that cleaves DNA into fragments at or near specific recognition sites within molecules known as restriction sites. Restriction enzymes are one class o ...
and comparing the resulting digestion patterns by gel electrophoresis.


Detection

Epstein–Barr virus-encoded small RNAs (EBERs) are by far the most abundant EBV products transcribed in cells infected by EBV. They are commonly used as targets for the detection of EBV in histological tissues.


Role in disease

:''See also
Infectious mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adult ...
and the other diseases listed in this section'' EBV causes infectious mononucleosis. Children infected with EBV have few symptoms or can appear asymptomatic, but when infection is delayed to adolescence or adulthood, it can cause fatigue,
fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
, inflamed throat,
swollen Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...
lymph nodes A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
in the neck, enlarged spleen, swollen liver, or rash. Post-infectious chronic fatigue syndrome has also been associated with EBV infection. EBV has also been implicated in several other diseases, including Burkitt's lymphoma,
hemophagocytic lymphohistiocytosis Hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis (British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a ...
,
Hodgkin's lymphoma Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition w ...
, stomach cancer, nasopharyngeal carcinoma, multiple sclerosis, and lymphomatoid granulomatosis. Specifically, EBV infected B-cells have been shown to reside within the brain lesions of multiple sclerosis patients, and a 2022 study of 10 million soldiers' historical blood samples showed that "Individuals who were not infected with the Epstein-Barr virus virtually never get multiple sclerosis. It's only after Epstein-Barr virus infection that the risk of multiple sclerosis jumps up by over 30-fold," and that only EBV of many infections had such a clear connection with the disease. Additional diseases that have been linked to EBV include Gianotti–Crosti syndrome,
erythema multiforme Erythema multiforme (EM) is a skin condition that appears with red patches evolving into target lesions, typically on both hands. It is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in th ...
, acute genital ulcers, and oral hairy leukoplakia. The viral infection is also associated with, and often contributes to the development of, a wide range of non-malignant lymphoproliferative diseases such as severe hypersensitivity mosquito bite allergy reactions, Epstein-Barr virus-positive mucocutaneous ulcers, and
hydroa vacciniforme Hydroa vacciniforme (HV) is a very rare, chronic photodermatitis-type skin condition with usual onset in childhood. It was first described in 1862 by Pierre-Antoine-Ernest Bazin. It is sometimes called "Bazin's hydroa vacciniforme". A study publish ...
as well as malignant lymphoproliferative diseases such as Epstein–Barr virus-positive Burkitt lymphoma, Epstein–Barr virus-positive Hodgkin lymphoma, and
primary effusion lymphoma Primary effusion lymphoma (PEL) is classified as a diffuse large B cell lymphoma. It is a rare malignancy of plasmablastic cells that occurs in individuals that are infected with the Kaposi's sarcoma-associated herpesvirus (i.e. KSHV/HHV8). Plasmab ...
. The Epstein–Barr virus has been implicated in disorders related to
alpha-synuclein Alpha-synuclein is a protein that, in humans, is encoded by the ''SNCA'' gene. Alpha-synuclein is a neuronal protein that regulates synaptic vesicle trafficking and subsequent neurotransmitter release. It is abundant in the brain, while smaller a ...
aggregation (e.g.
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
,
dementia with Lewy bodies Dementia with Lewy bodies (DLB) is a type of dementia characterized by changes in sleep, behavior, cognition, movement, and regulation of automatic bodily functions. Memory loss is not always an early symptom. The disease worsens over time an ...
, and multiple system atrophy).


History

The Epstein–Barr virus was named after Michael Anthony Epstein, and Yvonne Barr, who discovered the virus together with Bert Achong. In 1961, Epstein, a
pathologist Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in t ...
and expert electron microscopist, attended a lecture on "The Commonest Children's Cancer in Tropical Africa—A Hitherto Unrecognised Syndrome" by Denis Parsons Burkitt, a surgeon practicing in
Uganda }), is a landlocked country in East Africa. The country is bordered to the east by Kenya, to the north by South Sudan, to the west by the Democratic Republic of the Congo, to the south-west by Rwanda, and to the south by Tanzania. The sou ...
, in which Burkitt described the "endemic variant" (pediatric form) of the disease that bears his name. In 1963, a specimen was sent from Uganda to
Middlesex Hospital Middlesex Hospital was a teaching hospital located in the Fitzrovia area of London, England. First opened as the Middlesex Infirmary in 1745 on Windmill Street, it was moved in 1757 to Mortimer Street where it remained until it was finally clos ...
to be cultured. Virus particles were identified in the cultured cells, and the results were published in ''
The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal and one of the oldest of its kind. It is also the world's highest-impact academic journal. It was founded in England in 1823. The journal publishes original research articles, ...
'' in 1964 by Epstein, Achong, and Barr. Cell lines were sent to Werner and Gertrude Henle at the
Children's Hospital of Philadelphia The Children's Hospital of Philadelphia (CHOP) is a children's hospital in Philadelphia, Pennsylvania, with its primary campus located in the University City neighborhood of West Philadelphia in the campus of the University of Pennsylvania. The ...
who developed
serological Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mic ...
markers. In 1967, a technician in their laboratory developed mononucleosis and they were able to compare a stored serum sample, showing that antibodies to the virus developed. In 1968, they discovered that EBV can directly immortalize B cells after infection, mimicking some forms of EBV-related infections, and confirmed the link between the virus and infectious mononucleosis.


Research

As a relatively complex virus, EBV is not yet fully understood. Laboratories around the world continue to study the virus and develop new ways to treat the diseases it causes. One popular way of studying EBV ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
'' is to use
bacterial artificial chromosome A bacterial artificial chromosome (BAC) is a DNA construct, based on a functional fertility plasmid (or F-plasmid), used for transforming and cloning in bacteria, usually '' E. coli''. F-plasmids play a crucial role because they contain partiti ...
s. Epstein–Barr virus can be maintained and manipulated in the laboratory in continual latency (a property shared with
Kaposi's sarcoma-associated herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is ''Human gammaherpesvirus 8'', or HHV-8 in short. Like other herpesvir ...
, another of the eight human herpesviruses). Although many viruses are assumed to have this property during infection of their natural hosts, there is not an easily managed system for studying this part of the viral lifecycle. Genomic studies of EBV have been able to explore lytic reactivation and regulation of the latent viral episome. Although under active research, an Epstein–Barr virus vaccine is not yet available. The development of an effective vaccine could prevent up to 200,000 cancers globally per year. The absence of effective animal models is an obstacle to development of prophylactic and therapeutic vaccines against EBV. Like other human herpesviruses Epstein-Barr might allow eradication via a course of the pro-drug valaciclovir, but further research is needed to determine if eradication is actually achievable. Antiviral agents act by inhibiting viral DNA replication, but there is little evidence that they are effective against Epstein–Barr virus. Moreover, they are expensive, risk causing resistance to antiviral agents, and (in 1% to 10% of cases) can cause unpleasant
side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
s.


See also

* Epstein–Barr virus infection * Epstein–Barr virus-associated lymphoproliferative diseases * James Corson Niederman, the physician who proved how the Epstein–Barr virus is transmitted in infectious mononucleosis


References


Further reading

*


External links

* *
Transcriptome and epigenome of EBV
{{DEFAULTSORT:Epstein-Barr Virus Betaherpesvirinae IARC Group 1 carcinogens Infectious causes of cancer Viral diseases