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Epstein–Barr virus

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Epstein–Barr virus

The Epstein–Barr virus (EBV), also known as human herpesvirus 4 (HHV-4), 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. EBV is the first identified oncogenic virus, a virus that can cause cancer. EBV establishes a permanent infection in human B cells. It is the most common cause (90% of cases) of infectious mononucleosis and is also tightly linked to many malignant diseases (cancers and autoimmune diseases). Various vaccine formulations have been tested in humans and other animals, however none of them were able to prevent EBV infection; thus, no vaccine has been approved to date. Infectious mononucleosis ("mono" or "glandular fever"), is characterized by extreme fatigue, fever, sore throat, and swollen lymph nodes. EBV is also associated with various non-malignant, premalignant, and malignant EBV-associated lymphoproliferative diseases such as Burkitt lymphoma, hemophagocytic lymphohistiocytosis, and Hodgkin's lymphoma; non-lymphoid malignancies such as gastric cancer and nasopharyngeal carcinoma; and conditions associated with human immunodeficiency virus such as hairy leukoplakia and central nervous system lymphomas. The virus is also associated with the childhood disorders of Alice in Wonderland syndrome and acute cerebellar ataxia and, by some evidence, higher risks of developing certain autoimmune diseases, especially dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome. About 200,000 cancer cases globally per year are thought to be attributable to EBV. In 2022, a large study following 10 million active US military over 20 years suggested EBV as the leading cause of multiple sclerosis (MS), with a recent EBV infection causing a 32-fold increase in MS risk development. Infection with EBV occurs by the oral transfer of saliva and genital secretions. Most people become infected with EBV and gain adaptive immunity. 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. Most children who become infected with EBV display no symptoms, or the symptoms are indistinguishable from other mild, brief illnesses of childhood. When infection occurs during adolescence or young adulthood, it causes infectious mononucleosis 35 to 50% of the time. EBV infects B cells of the immune system and epithelial cells, and may infect T cells, NK cells, and histiocytic-dendritic 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.

Tables

· Virology › Replication cycle › Latency
Product
Product
Gene Expressed
Product
EBNA-1
Protein
EBNA-2
Protein
EBNA-3A
Protein
EBNA-3B
Protein
EBNA-3C
Protein
EBNA-LP
Protein
LMP1
Protein
LMP-2A
Protein
LMP-2B
Protein
EBER
ncRNAs
Latency I
Latency I
Gene Expressed
Latency I
EBNA-1
+
EBNA-2
EBNA-3A
EBNA-3B
EBNA-3C
EBNA-LP
LMP1
LMP-2A
LMP-2B
EBER
+
Latency II
Latency II
Gene Expressed
Latency II
EBNA-1
+
EBNA-2
EBNA-3A
EBNA-3B
EBNA-3C
EBNA-LP
+
LMP1
+
LMP-2A
+
LMP-2B
+
EBER
+
Latency III
Latency III
Gene Expressed
Latency III
EBNA-1
+
EBNA-2
+
EBNA-3A
+
EBNA-3B
+
EBNA-3C
+
EBNA-LP
+
LMP1
+
LMP-2A
+
LMP-2B
+
EBER
+
Gene Expressed
EBNA-1
EBNA-2
EBNA-3A
EBNA-3B
EBNA-3C
EBNA-LP
LMP1
LMP-2A
LMP-2B
EBER
Product
Protein
Protein
Protein
Protein
Protein
Protein
Protein
Protein
Protein
ncRNAs
Latency I
+
+
Latency II
+
+
+
+
+
+
Latency III
+
+
+
+
+
+
+
+
+
+
· Virology › Protein/genes
EBNA-1
EBNA-1
Protein/gene/antigen
EBNA-1
Stage
latent+lytic
Description
EBNA-1 protein binds to a replication origin (oriP) within the viral genome and mediates replication and partitioning of the episome during division of the host cell. It is the only viral protein expressed during group I latency.
EBNA-2
EBNA-2
Protein/gene/antigen
EBNA-2
Stage
latent+lytic
Description
EBNA-2 is the main viral transactivator.
EBNA-3
EBNA-3
Protein/gene/antigen
EBNA-3
Stage
latent+lytic
Description
These genes also bind the host RBP-Jκ protein.
LMP-1
LMP-1
Protein/gene/antigen
LMP-1
Stage
latent
Description
LMP-1 is a six-span transmembrane protein that is also essential for EBV-mediated growth transformation.
LMP-2
LMP-2
Protein/gene/antigen
LMP-2
Stage
latent
Description
LMP-2A/LMP-2B are transmembrane proteins that act to block tyrosine kinase signaling.
EBER
EBER
Protein/gene/antigen
EBER
Stage
latent
Description
EBER-1/EBER-2 are small nuclear RNAs, which bind to certain nucleoprotein particles, enabling binding to PKR (dsRNA-dependent serin/threonin protein kinase), thus inhibiting its function. EBERs are by far the most abundant EBV products transcribed in EBV-infected cells. They are commonly used as targets for the detection of EBV in histological tissues. ER-particles also induce the production of IL-10, which enhances growth and inhibits cytotoxic T cells.
v-snoRNA1
v-snoRNA1
Protein/gene/antigen
v-snoRNA1
Stage
latent
Description
Epstein–Barr virus snoRNA1 is a box CD-snoRNA generated by the virus during latency. V-snoRNA1 may act as a miRNA-like precursor that is processed into 24 nucleotide sized RNA fragments that target the 3'UTR of viral DNA polymerase mRNA.
ebv-sisRNA
ebv-sisRNA
Protein/gene/antigen
ebv-sisRNA
Stage
latent
Description
Ebv-sisRNA-1 is a stable intronic sequence RNA generated during latency program III. After the EBERs, it is the third-most abundant small RNA produced by the virus during this program.
miRNAs
miRNAs
Protein/gene/antigen
miRNAs
Stage
latent
Description
EBV microRNAs are encoded by two transcripts, one set in the BART gene and one set near the BHRF1 cluster. The three BHRF1 pri-miRNAS (generating four miRNAs) are expressed during type III latency, whereas the large cluster of BART miRNAs (up to 20 miRNAs) is expressed highly during type II latency and only modestly during type I and II latency. The previous reference also gives an account of the known functions of these miRNAs.
EBV-EA
EBV-EA
Protein/gene/antigen
EBV-EA
Stage
lytic
Description
early antigen
EBV-MA
EBV-MA
Protein/gene/antigen
EBV-MA
Stage
lytic
Description
membrane antigen
EBV-VCA
EBV-VCA
Protein/gene/antigen
EBV-VCA
Stage
lytic
Description
viral capsid antigen
EBV-AN
EBV-AN
Protein/gene/antigen
EBV-AN
Stage
lytic
Description
alkaline nuclease
Protein/gene/antigen
Stage
Description
EBNA-1
latent+lytic
EBNA-1 protein binds to a replication origin (oriP) within the viral genome and mediates replication and partitioning of the episome during division of the host cell. It is the only viral protein expressed during group I latency.
EBNA-2
latent+lytic
EBNA-2 is the main viral transactivator.
EBNA-3
latent+lytic
These genes also bind the host RBP-Jκ protein.
LMP-1
latent
LMP-1 is a six-span transmembrane protein that is also essential for EBV-mediated growth transformation.
LMP-2
latent
LMP-2A/LMP-2B are transmembrane proteins that act to block tyrosine kinase signaling.
EBER
latent
EBER-1/EBER-2 are small nuclear RNAs, which bind to certain nucleoprotein particles, enabling binding to PKR (dsRNA-dependent serin/threonin protein kinase), thus inhibiting its function. EBERs are by far the most abundant EBV products transcribed in EBV-infected cells. They are commonly used as targets for the detection of EBV in histological tissues. ER-particles also induce the production of IL-10, which enhances growth and inhibits cytotoxic T cells.
v-snoRNA1
latent
Epstein–Barr virus snoRNA1 is a box CD-snoRNA generated by the virus during latency. V-snoRNA1 may act as a miRNA-like precursor that is processed into 24 nucleotide sized RNA fragments that target the 3'UTR of viral DNA polymerase mRNA.
ebv-sisRNA
latent
Ebv-sisRNA-1 is a stable intronic sequence RNA generated during latency program III. After the EBERs, it is the third-most abundant small RNA produced by the virus during this program.
miRNAs
latent
EBV microRNAs are encoded by two transcripts, one set in the BART gene and one set near the BHRF1 cluster. The three BHRF1 pri-miRNAS (generating four miRNAs) are expressed during type III latency, whereas the large cluster of BART miRNAs (up to 20 miRNAs) is expressed highly during type II latency and only modestly during type I and II latency. The previous reference also gives an account of the known functions of these miRNAs.
EBV-EA
lytic
early antigen
EBV-MA
lytic
membrane antigen
EBV-VCA
lytic
viral capsid antigen
EBV-AN
lytic
alkaline nuclease
Interpretation of specific EBV antibodies · Detection
Never infected
Never infected
Typical interpretation
Never infected
VCA-IgG
VCA-IgM
EA
EBNA
Acute infection (IM)
Acute infection (IM)
Typical interpretation
Acute infection (IM)
VCA-IgG
+
VCA-IgM
+
EA
+/−
EBNA
Acute or recent infection
Acute or recent infection
Typical interpretation
Acute or recent infection
VCA-IgG
+
VCA-IgM
+/−
EA
+
EBNA
+/−
Recent past infection
Recent past infection
Typical interpretation
Recent past infection
VCA-IgG
+
VCA-IgM
EA
+/−
EBNA
+
Distant past infection
Distant past infection
Typical interpretation
Distant past infection
VCA-IgG
+
VCA-IgM
EA
EBNA
+
Chronic infection/reactivation
Chronic infection/reactivation
Typical interpretation
Chronic infection/reactivation
VCA-IgG
+
VCA-IgM
EA
+
EBNA
+/−
Typical interpretation
VCA-IgG
VCA-IgM
EA
EBNA
Never infected
Acute infection (IM)
+
+
+/−
Acute or recent infection
+
+/−
+
+/−
Recent past infection
+
+/−
+
Distant past infection
+
+
Chronic infection/reactivation
+
+
+/−

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