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a harmful or corrupting agency; "bigotry is a virus that must not be allowed to spread"; "the virus of jealousy is latent in everyone"
(virology) ultramicroscopic infectious agent that replicates itself only within cells of living hosts; many are pathogenic; a piece of nucleic acid (DNA or RNA) wrapped in a thin coat of protein
a software program capable of reproducing itself and usually capable of causing great harm to files or other programs on the same computer; "a true virus cannot spread to another computer without human assistance" (同)computer virus
the 5th letter of the Roman alphabet (同)e

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ビールス,ろ過性病原体

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/08/09 13:41:49」(JST)

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The Epstein–Barr virus (EBV), also called human herpesvirus 4 (HHV-4), is a virus of the herpes family, and is one of the most common viruses in humans.

It is best known as the cause of infectious mononucleosis (glandular fever). It is also associated with particular forms of cancer, such as Hodgkin's lymphoma, Burkitt's lymphoma, nasopharyngeal carcinoma, and conditions associated with human immunodeficiency virus (HIV) such as hairy leukoplakia and central nervous system lymphomas.^[1]^[2] There is evidence that infection with the virus is associated with a higher risk of certain autoimmune diseases,^[3] especially dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome,^[4]^[5] and multiple sclerosis.^[6]

Infection with EBV occurs by the oral transfer of saliva^[7] 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 90 to 95 percent of adults have evidence of previous infection.^[8] 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 teenage years, it causes infectious mononucleosis 35 to 50 percent of the time.^[9]

EBV infects B cells of the immune system and epithelial cells. Once the virus's initial lytic infection is brought under control, EBV latently persists in the individual's B cells for the rest of the individual's life.^[7]

1 Virology
- 1.1 Structure and genome
- 1.2 Tropism
- 1.3 Replication cycle
  - 1.3.1 Entry to the cell
  - 1.3.2 Lytic replication
  - 1.3.3 Latency
  - 1.3.4 Reactivation
- 1.4 Transformation of B-lymphocytes
- 1.5 Latent antigens
- 1.6 Protein/genes
- 1.7 Subtypes of EBV
2 Role in disease
3 History
4 Research
5 References

Virology[edit source | edit]

Structure and genome[edit source | edit]

A mature EBV viral particle has a diameter of approximately 120 nm to 180 nm. It is composed of a double stranded, linear DNA genome enclosed by a protein capsid. The capsid is surrounded by a protein tegument, which in turn is surrounded by a lipid envelope.^[10]

The EBV genome is about 192 thousand base pairs in length and contains about 85 genes.^[7]

The viral envelope is embedded with glycoproteins essential to viral entry into the cell.^[10]

In laboratory and animal trials in 2000, it was shown that both antagonism of RA-mediated growth inhibition and promotion of LCL proliferation were efficiently reversed by the glucocorticoid receptor (GR) antagonist RU486.^[11]

The Epstein–Barr virus transcriptome and epigenome have been extensively mapped.^[12]

Tropism[edit source | edit]

The term viral tropism refers to which cell types EBV infects. EBV can infect a number of different cell types, including B cells and epithelial cells. Under certain cases, it may infect T cells, natural killer cells, and smooth muscle cells.

The viral three-part glycoprotein complexes of gHgLgp42 mediate B cell membrane fusion; while the two-part complexes of gHgL mediate epithelial cell membrane fusion. EBV that are made in the B cells have low numbers of the gHgLgp42 complexes as the three-part complexes interact with HLA class II 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 have MHC class II. As a result, EBV made from B cells are more infectious to epithelial cells, and EBV made from epithelial cells are more infectious to B cells.

Replication cycle[edit source | edit]

The EBV replication cycle

Entry to the cell[edit source | edit]

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 (also known as CR2).^[13] Then, viral glycoprotein gp42 interacts with cellular MHC class II molecules. This triggers fusion of the viral envelope with the cell membrane, allowing EBV to enter the B cell.^[10]

To enter epithelial cells, viral protein BMRF-2 interacts with cellular β1 integrins. Then, viral protein gH/gL interacts with cellular αvβ6/8 integrins. This triggers fusion of the viral envelope with the epithelial cell membrane, allowing EBV to enter the epithelial cell.^[10] Unlike B cell entry, epithelial cell entry is actually impeded by viral glycoprotein gp42.^[13]

Once EBV enters the cell, the viral capsid dissolves and the viral genome is transported to the cell nucleus.

Lytic replication[edit source | edit]

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.^[10]

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 is responsible for copying the viral genome. This contrasts with latency, in which host cell DNA polymerase copies the viral genome.^[10]

Lytic gene products are produced in three consecutive stages: immediate-early, early, and late.^[10] Immediate-early lytic gene products act as transactivators, enhancing the expression of later lytic genes. Immediate-early lytic gene products include BZLF1 (also known as Zta and ZEBRA) and BRLF1.^[10] Early lytic gene products have many more functions, such as replication, metabolism, and blockade of antigen processing. Early lytic gene products include BNLF2.^[10] Finally, late lytic gene products tend to be proteins with structural roles, like VCA, which forms the viral capsid. Other late lytic gene products, such as BCRF1, help EBV evade the immune system.^[10]

Unlike lytic replication for many other viruses, EBV lytic replication does not inevitably lead to lysis of the host cell because EBV virions are produced by budding from the infected cell. Lytic proteins include gp350 and gp110.^[10]^[14]

Latency[edit source | edit]

Unlike lytic replication, latency does not result in production of virions.^[10] Instead, the EBV genome circularizes, resides in the cell nucleus as an episome, and is copied by cellular DNA polymerase.^[10] In latency, only a portion of EBV's genes are expressed.^[7] Latent EBV expresses its genes in one of three patterns, known as latency programs. EBV can latently persist within B cells and epithelial cells, 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.^[15]^[16]

Gene Expressed	EBNA-1	EBNA-2	EBNA-3A	EBNA-3B	EBNA-3C	EBNA-LP	LMP-1	LMP-2A	LMP-2B	EBER
Product	Protein	Protein	Protein	Protein	Protein	Protein	Protein	Protein	Protein	ncRNAs
Latency I	+	–	–	–	–	–	–	–	–	+
Latency II	+	–	–	–	–	+	+	+	+	+
Latency III	+	+	+	+	+	+	+	+	+	+

It is also postulated that a program exists in which all viral protein expression is shut off (Latency 0).

Within B cells, all three latency programs are possible.^[7] 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.^[7] 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).^[7]^[10] 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.^[7]^[10] 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.^[7]^[10]

Within epithelial cells, only Latency II is possible.^{[citation needed]}

In primary infection, EBV replicates in oro-pharyngeal 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.^[17]

Reactivation[edit source | edit]

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 reactivation in vivo probably takes place when latently infected B cells respond to unrelated infections.^[10] In vitro, latent EBV in B cells can also be reactivated by treating the cells with sodium butyrate or TPA.^{[citation needed]}

Transformation of B-lymphocytes[edit source | edit]

When EBV infects B cells in vitro, 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, while EBNA-LP and the EBERs are not.^[18]

It is postulated that following natural infection with EBV, the virus executes 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 amounts of virus 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.^[19]

Latent antigens[edit source | edit]

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 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[edit source | edit]

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. EBER-particles also induce the production of IL-10 which enhances growth and inhibits cytotoxic T-cells.
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 miRNAS are expressed during type III latency while the large cluster of BART miRNAs (up to 20 miRNAs) are expressed during type II latency. The functions of these miRNAs are currently unknown.
EBV-EA	lytic	early antigen
EBV-MA	lytic	membrane antigen
EBV-VCA	lytic	viral capsid antigen
EBV-AN	lytic	alkaline nuclease^[20]^[21]

Subtypes of EBV[edit source | edit]

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. One can distinguish EBV type 1 from EBV type 2 by cutting the viral genome with a restriction enzyme and comparing the resulting digestion patterns by gel electrophoresis.^[10]

Role in disease[edit source | edit]

EBV has been implicated in several diseases that include infectious mononucleosis, Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma and multiple sclerosis.^[6]

History[edit source | edit]

Epstein–Barr virus is named after Michael Anthony Epstein, Professor Emeritus at the University of Bristol and Yvonne Barr (born 1932 in London), graduated from the University of London in 1966 with a Ph.D, who discovered and documented the virus.^[22] In 1961, Epstein, a pathologist and expert electron microscopist, attended a lecture on "The Commonest Children's Cancer in Tropical Africa—A Hitherto Unrecognised Syndrome." This lecture, by Denis Parsons Burkitt, a surgeon practicing in Uganda, was the description of the "endemic variant" (pediatric form) of the disease that bears his name. In 1963, a specimen was sent from Uganda to Middlesex Hospital to be cultured. Virus particles were identified in the cultured cells, and the results were published in The Lancet in 1964 by Epstein, Bert Achong, and Barr. Cell lines were sent to Werner and Gertrude Henle at the Children's Hospital of Philadelphia who developed serological 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.^[23]^[24]^[25] In 1968, they discovered that EBV can directly immortalize B cells after infection, mimicking some forms of EBV-related infections,^[26] and confirmed the link between the virus and infectious mononucleosis.^[27]

Research[edit source | edit]

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 is to use bacterial artificial chromosomes.^[28] Epstein–Barr virus and its sister virus KSHV can be maintained and manipulated in the laboratory in continual latency. While many viruses are assumed to have this property during infection of their natural host, they do not have 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.^[12]

References[edit source | edit]

^ Maeda E, Akahane M, Kiryu S, et al. (January 2009). "Spectrum of Epstein–Barr virus-related diseases: a pictorial review". Jpn J Radiol 27 (1): 4–19. doi:10.1007/s11604-008-0291-2. PMID 19373526.
^ Cherry-Peppers, G; Daniels, CO; Meeks, V; Sanders, CF; Reznik, D (2003 Feb). "Oral manifestations in the era of HAART.". Journal of the National Medical Association 95 (2 Suppl 2): 21S–32S. PMC 2568277. PMID 12656429.
^ Toussirot E, Roudier J (October 2008). "Epstein–Barr virus in autoimmune diseases". Best Practice & Research. Clinical Rheumatology 22 (5): 883–96. doi:10.1016/j.berh.2008.09.007. PMID 19028369.
^ Dreyfus DH (December 2011). "Autoimmune disease: A role for new anti-viral therapies?". Autoimmunity Reviews 11 (2): 88–97. doi:10.1016/j.autrev.2011.08.005. PMID 21871974.
^ Pender MP (2012). "CD8+ T-Cell Deficiency, Epstein–Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis". Autoimmune Diseases 2012: 189096. doi:10.1155/2012/189096. PMC 3270541. PMID 22312480.
^ ^a ^b Ascherio A, Munger KL (September 2010). "Epstein–Barr virus infection and multiple sclerosis: a review". Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology 5 (3): 271–7. doi:10.1007/s11481-010-9201-3. PMID 20369303.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Amon; Farrell (November 2004). "Reactivation of Epstein–Barr virus from latency". Reviews in Medical Virology. doi:10.1002/rmv.456. Retrieved 28 May 2012.
^ In the United States, as many as 95% of adults between 35 and 40 years of age have been infected. National Center for Infectious Diseases
^ CDC. "Epstein–Barr Virus and Infectious Mononucleosis". CDC. Retrieved 2011-12-29.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r Odumade; Hogquist, Balfour (January 2011). "Progress and Problems in Understanding and Managing Primary Epstein–Barr Virus Infections". American Society for Microbiology. doi:10.1128/CMR.00044-10. Retrieved 30 May 2012.
^ Quaia M, Zancai P, Cariati R, Rizzo S, Boiocchi M, Dolcetti R (July 2000). "Glucocorticoids promote the proliferation and antagonize the retinoic acid-mediated growth suppression of Epstein–Barr virus-immortalized B lymphocytes". Blood 96 (2): 711–8. PMID 10887139.
^ ^a ^b Arvey A, Tempera I, Tsai K, Chen HS, Tikhmyanova N, Klichinsky M, Leslie C, Lieberman PM (August 2012). "An atlas of the Epstein–Barr virus transcriptome and epigenome reveals host-virus regulatory interactions". Cell Host Microbe 12 (2): 233–245. doi:10.1016/j.chom.2012.06.008. PMID 22901543.
^ ^a ^b "Entrez Gene: CR2 complement component (3d/Epstein Barr virus) receptor 2".
^ Lockey TD, Zhan X, Surman S, Sample CE, Hurwitz JL (2008). "Epstein–Barr virus vaccine development: a lytic and latent protein cocktail". Front. Biosci. 13 (13): 5916–27. doi:10.2741/3126. PMID 18508632.
^ Calderwood MA, Venkatesan K, Xing L, Chase MR, Vazquez A, Holthaus AM, Ewence AE, Li N, Hirozane-Kishikawa T, Hill DE, Vidal M, Kieff E, Johannsen E (May 2007). "Epstein–Barr virus and virus human protein interaction maps". Proceedings of the National Academy of Sciences of the United States of America 104 (18): 7606–11. doi:10.1073/pnas.0702332104. PMC 1863443. PMID 17446270. The nomenclature used here is that of Kieff. Other laboratories use different nomenclatures.
^ Hutzinger R, Feederle R, Mrazek J, Schiefermeier N, Balwierz PJ, Zavolan M, Polacek N, Delecluse H, Hüttenhofer A (August 14, 2009). "Expression and Processing of a Small Nucleolar RNA from the Epstein–Barr Virus Genome". In Cullen, Bryan R. PLoS Pathogens 5 (8): e1000547. doi:10.1371/journal.ppat.1000547. PMC 2718842. PMID 19680535.
^ Robertson, ES (editor) (2010). Epstein–Barr Virus: Latency and Transformation. Caister Academic Press. ISBN 978-1-904455-62-2.
^ Yates JL, Warren N, Sugden B (1985). "Stable replication of plasmids derived from Epstein–Barr virus in various mammalian cells". Nature 313 (6005): 812–5. doi:10.1038/313812a0. PMID 2983224.
^ Gratama JW, Oosterveer MA, Zwaan FE, Lepoutre J, Klein G, Ernberg I (1988). "Eradication of Epstein–Barr virus by allogeneic bone marrow transplantation: implications for sites of viral latency". Proc. Natl. Acad. Sci. U.S.A. 85 (22): 8693–6. doi:10.1073/pnas.85.22.8693. PMC 282526. PMID 2847171.
^ Buisson M, Géoui T, Flot D, Tarbouriech N, Ressing ME, Wiertz EJ, Burmeister WP (2009). "A bridge crosses the active-site canyon of the Epstein–Barr virus nuclease with DNase and RNase activities". J Mol. Biol. 319 (4): 717–28. doi:10.1016/j.jmb.2009.06.034. PMID 19538972.
^ Buisson, M.; Géoui, T.; Flot, D.; Tarbouriech, N.; Ressing, M. E.; Wiertz, E. J.; Burmeister, W. P. (2009). "A Bridge Crosses the Active-Site Canyon of the Epstein–Barr Virus Nuclease with DNase and RNase Activities". Journal of Molecular Biology 391 (4): 717–728. doi:10.1016/j.jmb.2009.06.034. PMID 19538972. edit
^ M. A. Epstein, B. G. Achong, and Y. M. Barr: Virus particles in cultured lymphoblasts from Burkitt's lymphoma. The Lancet, March 28, 1964, 1: 702–703
^ Epstein, M. Anthony (2005). "1. The origins of EBV research: discovery and characterization of the virus". In Robertson, Earl S. Epstein–Barr Virus. Trowbridge: Cromwell Press. pp. 1–14. ISBN 1-904455-03-4. Retrieved September 18, 2010.
^ Erle S. Robertson (2005). Epstein-Barr Virus. Horizon Scientific Press. p. 18. ISBN 978-1-904455-03-5. Retrieved 3 June 2012.
^ Miller, George (December 21, 2006). "Book Review: Epstein–Barr Virus". New England Journal of Medicine 355 (25): 2708–2709. doi:10.1056/NEJMbkrev39523. Retrieved September 18, 2010.
^ Henle W, Henle G (1980). "Epidemiologic aspects of Epstein–Barr virus (EBV)-associated diseases". Annals of the New York Academy of Sciences 354: 326–31. PMID 6261650.
^ Young, LS (2009). Desk Encyclopedia of Human and Medical Virology. Boston: Academic Press. pp. 532–533.
^ Delecluse HJ, Feederle R, Behrends U, Mautner J (December 2008). "Contribution of viral recombinants to the study of the immune response against the Epstein–Barr virus". Seminars in Cancer Biology 18 (6): 409–15. doi:10.1016/j.semcancer.2008.09.001. PMID 18938248.

UpToDate Contents

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1. エプスタインバーウイルス（EBウイルス）感染の臨床的特徴および治療 clinical manifestations and treatment of epstein barr virus infection
2. エプスタインバーウイルス（EBウイルス）のウイルス学 virology of epstein barr virus
3. 成人および思春期の伝染性単核球症 infectious mononucleosis in adults and adolescents
4. ホジキンリンパ腫におけるエプスタイン・バール・ウイルス the role of epstein barr virus in hodgkin lymphoma
5. 移植後リンパ球増殖性疾患の疫学、臨床症状、および診断 epidemiology clinical manifestations and diagnosis of post transplant lymphoproliferative disorders

English Journal

Cancer stem-like cell characteristics induced by EB virus-encoded LMP1 contribute to radioresistance in nasopharyngeal carcinoma by suppressing the p53-mediated apoptosis pathway.

Yang CF1, Peng LX2, Huang TJ3, Yang GD2, Chu QQ4, Liang YY2, Cao X2, Xie P2, Zheng LS2, Huang HB5, Cai MD1, Huang JL6, Liu RY5, Zhu ZY7, Qian CN8, Huang BJ9.Author information 1Department of Cancer Chemotherapy, The People's Hospital of Gaozhou, Guangdong Province, China.2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China; Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, China.3Department of Nuclear Medicine, The Second People's Hospital of Shenzhen, Shenzhen, China.4School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.5State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.6Department of Medicine, Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, USA.7Department of Biochemistry & Molecular Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.8State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, China. Electronic address: qianchn@sysucc.org.cn.9State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China; Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, China. Electronic address: huangbj@sysucc.org.cn.AbstractEmerging evidence confirms that cancer stem cells (CSCs) are responsible for the chemoradioresistance of malignancies. EBV-encoded latent membrane protein 1 (LMP1) is associated with tumor relapse and poor prognosis of nasopharyngeal carcinoma (NPC). However, whether LMP1 induces the development of CSCs and the mechanism by which this rare cell subpopulation leads to radioresistance in NPC remain unclear. In the present study, LMP1-transformed NPC cells showed significant radioresistance compared to the empty vector control. We found that LMP1 up-regulated the expression of several stemness-related genes, increased the cell number of side population (SP) by flow cytometry analysis, enhanced the self-renewal properties of the cells in a spherical culture and enhanced the in vivo tumor initiation ability. We also found that LMP1 positively regulated the expression of the CSC marker CD44. The CD44(+/High) subpopulation of the LMP1-transformed NPC cells displayed more significant CSC characteristics than the CD44(-/Low) subpopulation of the LMP1-transformed NPC cells; these characteristics included the upregulation of stemness-related genes, in vitro self-renewal and in vivo tumor initiation ability. Importantly, the CD44(+/High) subpopulation displayed more radioresistance than the CD44(-/Low) subpopulation. Our results also demonstrated that phosphorylation of the DNA damage response (DDR) proteins, ATM, Chk1, Chk2 and p53, was inactivated in the LMP1-induced CD44(+/High) cells in response to DNA damage, and this was accompanied by a downregulation of the p53-targeted proapoptotic genes, which suggested that the inactivation of the p53-mediated apoptosis pathway was responsible for the radioresistance in the CD44(+/High) cells. Taken together, we found that LMP1 induced an increase in CSC-like CD44(+/High) cells, and we determined the molecular mechanism underlying the radioresistance of the LMP1-activated CSCs, highlighting the need of CSC-targeted radiotherapy in EBV-positive NPC.
Cancer letters.Cancer Lett.2014 Mar 28;344(2):260-71. doi: 10.1016/j.canlet.2013.11.006. Epub 2013 Nov 19.
Emerging evidence confirms that cancer stem cells (CSCs) are responsible for the chemoradioresistance of malignancies. EBV-encoded latent membrane protein 1 (LMP1) is associated with tumor relapse and poor prognosis of nasopharyngeal carcinoma (NPC). However, whether LMP1 induces the development of
PMID 24262659

Aquaporin-1 gene deletion reduces breast tumor growth and lung metastasis in tumor-producing MMTV-PyVT mice.

Esteva-Font C1, Jin BJ, Verkman AS.Author information 111246 Health Sciences East Tower, University of California, San Francisco, CA 94143-0521, USA. alan.verkman@ucsf.edu.AbstractAquaporin 1 (AQP1) is a plasma membrane water-transporting protein expressed strongly in tumor microvascular endothelia. We previously reported impaired angiogenesis in implanted tumors in AQP1-deficient mice and reduced migration of AQP1-deficient endothelial cells in vitro. Here, we investigated the consequences of AQP1 deficiency in mice that spontaneously develop well-differentiated, luminal-type breast adenomas with lung metastases [mouse mammary tumor virus-driven polyoma virus middle T oncogene (MMTV-PyVT)]. AQP1(+/+) MMTV-PyVT mice developed large breast tumors with total tumor mass 3.5 ± 0.5 g and volume 265 ± 36 mm(3) (se, 11 mice) at age 98 d. Tumor mass (1.6±0.2 g) and volume (131±15 mm(3), 12 mice) were greatly reduced in AQP1(-/-) MMTV-PyVT mice (P<0.005). CD31 immunofluorescence showed abnormal microvascular anatomy in tumors of AQP1(-/-) MMTV-PyVT mice, with reduced vessel density. HIF-1α expression was increased in tumors in AQP1(-/-) MMTV-PyVT mice. The number of lung metastases (5±1/mouse) was much lower than in AQP1(+/+) MMTV-PyVT mice (31±8/mouse, P<0.005). These results implicate AQP1 as an important determinant of tumor angiogenesis and, hence, as a potential drug target for adjuvant therapy of solid tumors.-Esteva-Font, C., Jin, B.-J., Verkman, A. S. Aquaporin-1 gene deletion reduces breast tumor growth and lung metastasis in tumor-producing MMTV-PyVT mice.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology.FASEB J.2014 Mar;28(3):1446-53. doi: 10.1096/fj.13-245621. Epub 2013 Dec 12.
Aquaporin 1 (AQP1) is a plasma membrane water-transporting protein expressed strongly in tumor microvascular endothelia. We previously reported impaired angiogenesis in implanted tumors in AQP1-deficient mice and reduced migration of AQP1-deficient endothelial cells in vitro. Here, we investigated t
PMID 24334548

Anti-tumor effects of an oncolytic adenovirus expressing hemagglutinin-neuraminidase of newcastle disease virus in vitro and in vivo.

He D1, Sun L2, Li C3, Hu N4, Sheng Y5, Chen Z6, Li X7, Chi B8, Jin N9.Author information 1Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, China. spring_101@163.com.2Head and Neck Surgery, The Tumor hospital of Jilin province, Changchun 130001, China. linjiaxiaoya@163.com.3Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122, China. lichang78@163.com.4Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122, China. 158795786@qq.com.5Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122, China. zjl55186666@qq.com.6Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122, China. zhifeic@163.com.7Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122, China. lixiao06@mails.jlu.edu.cn.8Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, China. chibr@jlu.edu.cn.9Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122, China. skylee528112@gmail.com.AbstractOncolytic virotherapy has been an attractive drug platform for targeted therapy of cancer over the past few years. Viral vectors can be used to target and lyse cancer cells, but achieving good efficacy and specificity with this treatment approach is a major challenge. Here, we assessed the ability of a novel dual-specific anti-tumor oncolytic adenovirus, expressing the hemagglutinin-neuraminidase (HN) gene from the Newcastle disease virus under the human telomerase reverse transcriptase (hTERT) promoter (Ad-hTERTp-E1a-HN), to inhibit esophageal cancer EC-109 cells in culture and to reduce tumor burden in xenografted BALB/c nude mice. In vitro, infection with Ad-hTERT-E1a-HN could inhibit the growth of EC-109 cells significantly and also protect normal human liver cell line L02 from growth suppression in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Ad-hTERT-E1a-HN also effectively and selectively decreased the sialic acid level on EC-109 cells, but not on L02 cells. Furthermore, Ad-hTERT-E1a-HN was shown to induce the apoptosis pathway via acridine orange and ethidium bromide staining (AO/EB staining), increase reactive oxygen species (ROS), reduce mitochondrial membrane potential and release cytochrome c. In vivo, xenografted BALB/c nude mice were treated via intratumoral or intravenous injections of Ad-hTERT-E1a-HN. Although both treatments showed an obvious suppression in tumor volume, only Ad-hTERT-E1a-HN delivered via intratumoral injection elicited a complete response to treatment. These results reinforced previous findings and highlighted the potential therapeutic application of Ad-hTERT-E1a-HN for treatment of esophageal cancer in clinical trials.
Viruses.Viruses.2014 Feb 18;6(2):856-74. doi: 10.3390/v6020856.
Oncolytic virotherapy has been an attractive drug platform for targeted therapy of cancer over the past few years. Viral vectors can be used to target and lyse cancer cells, but achieving good efficacy and specificity with this treatment approach is a major challenge. Here, we assessed the ability o
PMID 24553109

Japanese Journal

症例 γδT細胞にEBウイルスの感染がみられた種痘様水疱症

皮膚科の臨床 57(12), 1931-1935, 2015-11
NAID 40020654335

EBVと造血器腫瘍 (第112回(2015年) 日本内科学会講演会イノベーションで拓く内科学) -- (シンポジウムウイルス感染と腫瘍)

日本内科学会雑誌 104(9), 1878-1884, 2015-09-10
NAID 40020595518

小児におけるEBV関連リンパ増殖性疾患 (特集ウイルス感染関連造血器疾患の病態・治療研究の進歩)

血液内科 = Hematology 71(2), 237-243, 2015-08
NAID 40020578829

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chronic active EB virus infection(CAEBV) - PukiWiki eb virus cz - DriverLayer Search Engine 先端血液検査学｜国立大学法人東京医科歯科大学｜医学部公式

★リンクテーブル★

リンク元	「EBウイルス」
拡張検索	「EB virus latent membrane protein」「EB virus-related marker」
関連記事	「EB」「E」「virus」

「EBウイルス」

Epstein–Barr
	Two Epstein–Barr virions
Virus classification
Group:	Group I (dsDNA)
Order:	Herpesvirales
Family:	Herpesviridae
Subfamily:	Gammaherpesvirinae
Genus:	Lymphocryptovirus
Species:	Human herpesvirus 4 (HHV-4)
Synonyms
	EB virus;

　　[★]

英: Epstein-Barr virus, EB virus, EBV
同: エプスタイン-バーウイルスエプスタイン-バー・ウイルス、エプスタイン・バーウイルス
関: EBウイルス感染症、ウイルス

ウイルス学

ヘルペスウイルス科ガンマヘルペスウイルス亜科リンフェクリプトウイルス属
二本鎖DNAウイルス。エンベロープあり。
ウイルスのレセプターはCD21
Bリンパ球に潜伏感染

EBV関連抗原

EA, early antigen
VCA, virus capsid antigen
EBNA, EB virus determined nuclear antigen
LMA, late membrane antigen
LYDMA, lymphocyte-detected membrane antigen

EBV特異抗体

感染症

伝染性単核球症：(小児期の初感染ではかぜ、あるいは不顕性感染(乳幼児では不顕性が多い))
バーキットリンパ腫：悪性リンパ腫。chr8, chr14の相互転座による染色体異常(BL細胞)c-mycの発現が活性化
B細胞リンパ腫(HIV感染者など)
NK細胞リンパ腫(097H066)
Duncan症候群(XLP)
慢性活動性EBV感染症(chronic active EBV infection)
エイズでの日和見感染。日和見Bリンパ腫
上咽頭癌：中国で多い
胃癌
口腔内白斑

感染経路

唾液感染

疫学

日本では3歳までに80%が感染する (SMB.530)

検査

急性期・回復期に、VCA-IGM, VCA-IgG, EA(早期抗原, early antigen)の高値、EBNA(核内抗原)の陰性を証明

EBNAは感染後3ヶ月以上経たないと立ち上がらない。

Paul-Bunnel反応(1週間40%, 4週間80-90%)

ウイルス抗体価：急性期（発病2～7日）と回復期（2～3週）の検体を同時測定し、回復期の抗体価が急性期の結果の4倍（2管差）以上に上昇したとき、血清学的に有意とみなす。

抗体のパターン

	VCA IgG	VCA IgM	EBNA	EA IgG
感染前	ー	ー	ー	ー
急性期	＋	＋	ー	＋／ー
回復期	＋	＋／ー	＋／ー	＋／ー
感染既往	＋	ー	＋	＋／ー
再活性化	＋	＋／ー	＋	＋

目的別検査組み合わせ

	VCA IgG	VCA IgM	EBNA	EA IgG	VCA IgA
伝染性単核症	○	○	○	○
EBV再活性化の疑い	○		○	○
既往確認	○		○
バーキットリンパ腫	○		○	○
上咽頭癌	○		○	○	○
慢性活動性EBV感染症	○			○	○
上記以外でのEBV感染疑い	○	○	○	○

「EB virus latent membrane protein」

　　[★] EBウイルス潜伏感染膜蛋白質

「EB virus-related marker」

　　[★] EBウイルス関連マーカー

「EB」

　　[★]

「E」

　　[★]

「virus」

　　[★] ウイルス

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[Cherry-Peppers_2003-2] Cherry-Peppers, G; Daniels, CO; Meeks, V; Sanders, CF; Reznik, D (2003 Feb). "Oral manifestations in the era of HAART.". Journal of the National Medical Association 95 (2 Suppl 2): 21S–32S. PMC 2568277. PMID 12656429.

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[pmid21871974-4] Dreyfus DH (December 2011). "Autoimmune disease: A role for new anti-viral therapies?". Autoimmunity Reviews 11 (2): 88–97. doi:10.1016/j.autrev.2011.08.005. PMID 21871974.

[pmid22312480-5] Pender MP (2012). "CD8+ T-Cell Deficiency, Epstein–Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis". Autoimmune Diseases 2012: 189096. doi:10.1155/2012/189096. PMC 3270541. PMID 22312480.

[pmid20369303-6] Ascherio A, Munger KL (September 2010). "Epstein–Barr virus infection and multiple sclerosis: a review". Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology 5 (3): 271–7. doi:10.1007/s11481-010-9201-3. PMID 20369303.

[Reactivation_of_Epstein-Barr_Virus-7] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Amon; Farrell (November 2004). "Reactivation of Epstein–Barr virus from latency". Reviews in Medical Virology. doi:10.1002/rmv.456. Retrieved 28 May 2012.

[CDC_.E2.80.93_Epstein.E2.80.93Barr_Virus_and_Infectious_Mononucleosis-8] In the United States, as many as 95% of adults between 35 and 40 years of age have been infected. National Center for Infectious Diseases

[9] CDC. "Epstein–Barr Virus and Infectious Mononucleosis". CDC. Retrieved 2011-12-29.

[Progress_and_Problems_in_Understanding-10] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r Odumade; Hogquist, Balfour (January 2011). "Progress and Problems in Understanding and Managing Primary Epstein–Barr Virus Infections". American Society for Microbiology. doi:10.1128/CMR.00044-10. Retrieved 30 May 2012.

[11] Quaia M, Zancai P, Cariati R, Rizzo S, Boiocchi M, Dolcetti R (July 2000). "Glucocorticoids promote the proliferation and antagonize the retinoic acid-mediated growth suppression of Epstein–Barr virus-immortalized B lymphocytes". Blood 96 (2): 711–8. PMID 10887139.

[pmid22901543-12] Arvey A, Tempera I, Tsai K, Chen HS, Tikhmyanova N, Klichinsky M, Leslie C, Lieberman PM (August 2012). "An atlas of the Epstein–Barr virus transcriptome and epigenome reveals host-virus regulatory interactions". Cell Host Microbe 12 (2): 233–245. doi:10.1016/j.chom.2012.06.008. PMID 22901543.

[entrez__1380-13] "Entrez Gene: CR2 complement component (3d/Epstein Barr virus) receptor 2".

[pmid18508632-14] Lockey TD, Zhan X, Surman S, Sample CE, Hurwitz JL (2008). "Epstein–Barr virus vaccine development: a lytic and latent protein cocktail". Front. Biosci. 13 (13): 5916–27. doi:10.2741/3126. PMID 18508632.

[pmid17446270-15] Calderwood MA, Venkatesan K, Xing L, Chase MR, Vazquez A, Holthaus AM, Ewence AE, Li N, Hirozane-Kishikawa T, Hill DE, Vidal M, Kieff E, Johannsen E (May 2007). "Epstein–Barr virus and virus human protein interaction maps". Proceedings of the National Academy of Sciences of the United States of America 104 (18): 7606–11. doi:10.1073/pnas.0702332104. PMC 1863443. PMID 17446270. The nomenclature used here is that of Kieff. Other laboratories use different nomenclatures.

[16] Hutzinger R, Feederle R, Mrazek J, Schiefermeier N, Balwierz PJ, Zavolan M, Polacek N, Delecluse H, Hüttenhofer A (August 14, 2009). "Expression and Processing of a Small Nucleolar RNA from the Epstein–Barr Virus Genome". In Cullen, Bryan R. PLoS Pathogens 5 (8): e1000547. doi:10.1371/journal.ppat.1000547. PMC 2718842. PMID 19680535.

[Robertsones-17] Robertson, ES (editor) (2010). Epstein–Barr Virus: Latency and Transformation. Caister Academic Press. ISBN 978-1-904455-62-2.

[Yates1985-18] Yates JL, Warren N, Sugden B (1985). "Stable replication of plasmids derived from Epstein–Barr virus in various mammalian cells". Nature 313 (6005): 812–5. doi:10.1038/313812a0. PMID 2983224.

[Gratama1988-19] Gratama JW, Oosterveer MA, Zwaan FE, Lepoutre J, Klein G, Ernberg I (1988). "Eradication of Epstein–Barr virus by allogeneic bone marrow transplantation: implications for sites of viral latency". Proc. Natl. Acad. Sci. U.S.A. 85 (22): 8693–6. doi:10.1073/pnas.85.22.8693. PMC 282526. PMID 2847171.

[Buisson2009-20] Buisson M, Géoui T, Flot D, Tarbouriech N, Ressing ME, Wiertz EJ, Burmeister WP (2009). "A bridge crosses the active-site canyon of the Epstein–Barr virus nuclease with DNase and RNase activities". J Mol. Biol. 319 (4): 717–28. doi:10.1016/j.jmb.2009.06.034. PMID 19538972.

[21] Buisson, M.; Géoui, T.; Flot, D.; Tarbouriech, N.; Ressing, M. E.; Wiertz, E. J.; Burmeister, W. P. (2009). "A Bridge Crosses the Active-Site Canyon of the Epstein–Barr Virus Nuclease with DNase and RNase Activities". Journal of Molecular Biology 391 (4): 717–728. doi:10.1016/j.jmb.2009.06.034. PMID 19538972. edit

[22] M. A. Epstein, B. G. Achong, and Y. M. Barr: Virus particles in cultured lymphoblasts from Burkitt's lymphoma. The Lancet, March 28, 1964, 1: 702–703

[23] Epstein, M. Anthony (2005). "1. The origins of EBV research: discovery and characterization of the virus". In Robertson, Earl S. Epstein–Barr Virus. Trowbridge: Cromwell Press. pp. 1–14. ISBN 1-904455-03-4. Retrieved September 18, 2010.

[Robertson2005-24] Erle S. Robertson (2005). Epstein-Barr Virus. Horizon Scientific Press. p. 18. ISBN 978-1-904455-03-5. Retrieved 3 June 2012.

[25] Miller, George (December 21, 2006). "Book Review: Epstein–Barr Virus". New England Journal of Medicine 355 (25): 2708–2709. doi:10.1056/NEJMbkrev39523. Retrieved September 18, 2010.

[pmid6261650-26] Henle W, Henle G (1980). "Epidemiologic aspects of Epstein–Barr virus (EBV)-associated diseases". Annals of the New York Academy of Sciences 354: 326–31. PMID 6261650.

[isbn0-12-375147-0-27] Young, LS (2009). Desk Encyclopedia of Human and Medical Virology. Boston: Academic Press. pp. 532–533.

[pmid18938248-28] Delecluse HJ, Feederle R, Behrends U, Mautner J (December 2008). "Contribution of viral recombinants to the study of the immune response against the Epstein–Barr virus". Seminars in Cancer Biology 18 (6): 409–15. doi:10.1016/j.semcancer.2008.09.001. PMID 18938248.

匿名

検索

案内

EB virus