Epstein Barr virus: Difference between revisions

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The human herpesvirus Epstein-Barr virus (EBV) establishes latency and promotes the long-term survival of its host B cell by targeting the molecular machinery controlling cell fate decisions. The cellular antiapoptotic bfl-1 gene confers protection from apoptosis under conditions of growth factor deprivation when expressed ectopically in an EBV-negative Burkitt's lymphoma-derived cell line (), and the EBV latent membrane protein 1 (LMP1) and its cellular functional homologue CD40 can both drive bfl-1 via an NF-B-dependent enhancer element in the bfl-1 promoter (B. N. D'Souza, L. C. Edelstein, P. M. Pegman, S. M. Smith, S. T. Loughran, A. Clarke, A. Mehl, M. Rowe, C. Gélinas, and D. Walls, J. Virol. 78:1800-1816, 2004). Here we show that the EBV nuclear antigen 2 (EBNA2) also upregulates bfl-1. EBNA2 trans-activation of bfl-1 requires CBF1 (or RBP-J), a nuclear component of the Notch signaling pathway, and there is an essential role for a core consensus CBF1-binding site on the bfl-1 promoter. trans-activation is dependent on the EBNA2-CBF1 interaction, is modulated by other EBV gene products known to interact with the CBF1 corepressor complex, and does not involve activation of NF-B. bfl-1 expression is induced and maintained at high levels by the EBV growth program in a lymphoblastoid cell line, and withdrawal of either EBNA2 or LMP1 does not lead to a reduction in bfl-1 mRNA levels in this context, whereas the simultaneous loss of both EBV proteins results in a major decrease in bfl-1 expression. These findings are relevant to our understanding of EBV persistence, its role in malignant disease, and the B-cell developmental process.
(). Here we show that the EBV nuclear antigen 2 (EBNA2) also upregulates bfl-1. EBNA2 trans-activation of bfl-1 requires CBF1 (or RBP-J), a nuclear component of the Notch signaling pathway, and there is an essential role for a core consensus CBF1-binding site on the bfl-1 promoter. trans-activation is dependent on the EBNA2-CBF1 interaction, is modulated by other EBV gene products known to interact with the CBF1 corepressor complex, and does not involve activation of NF-B. bfl-1 expression is induced and maintained at high levels by the EBV growth program in a lymphoblastoid cell line, and withdrawal of either EBNA2 or LMP1 does not lead to a reduction in bfl-1 mRNA levels in this context, whereas the simultaneous loss of both EBV proteins results in a major decrease in bfl-1 expression. These findings are relevant to our understanding of EBV persistence, its role in malignant disease, and the B-cell developmental process.


==Current Research==
==Current Research==

Revision as of 14:29, 6 April 2008

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Classification

Higher order taxa

Domain; Phylum; Class; Order; Herpesviridae [Others may be used. Use Tree of Life link to find]

Species

Lymphocryptovirus Human herpesvirus 4

Description and significance

Describe the appearance, habitat, etc. of the organism, and why it is important enough to have its genome sequenced. Describe how and where it was isolated. Include a picture or two (with sources) if you can find them.

The Epstein-Barr virus is a memeber of the herpesvirus family. EBV is one of the most common human viruses that occurs worldwide. At one time in their lives most people become infected with the EBV. In the United State, between the ages of 35 and 40 years 95 percent of adults have been infected by the virus. When adolescents and young adults are infected with EBV, infectious mononucleosis is cause 35-50 percent of the time.

Genome structure

Describe the size and content of the genome. How many chromosomes? Circular or linear? Other interesting features? What is known about its sequence? Does it have any plasmids? Are they important to the organism's lifestyle?

The B95-5 strain of the Epstein-Barr virus is comprised of 172,282 base pairs. Through mapping, likely regions of protein-coding have been found to encode for a ribonucleotide reductase, a DNA polymerase and two surface glycoproteins

Cell structure and metabolism

Describe any interesting features and/or cell structures; how it gains energy; what important molecules it produces.

The gp42 glycoprotein of the EBV binds to MHC class II molecules. This binding is important in the process of infecting the B lymphocytes. Gp42 glycoprotein belongs to the C-type lectin superfamily and has a crystal structure bound to the human MHC class II molecule HLA-DR1. The EBV gp42 binds to HLA-DR1 using a distinct surface site, which forms a hydrophobic groove and the canonical ligan binding site. This hydrophobic groove can avoid coupling mechanisms for MHC recognition and memabrane fusion, by interacting with other ligands necessary for EBV virus entry.

Ecology

Describe any interactions with other organisms (included eukaryotes), contributions to the environment, effect on environment, etc.

The EBV has a ubiquitous and uniform epidemiological distribution. The strategy of the virus is to guarentee transmission through persistence and continuous replication. These two characteristics of the virus occur in the B lymphocytes where latency takes place and in the epithelial cells where replication occurs, EBV-associated malignacies could potentially take place in these cellular compartments.

Pathology

How does this organism cause disease? Human, animal, plant hosts? Virulence factors, as well as patient symptoms.

The Epstein-Barr virus can cause infectious mononucleosis. Infectious mononucleosis can be contracted when a person is in pre to early adolescence. The transmission of mononuleosis can occur through the transfer of saliva and also through contact with the virus when it is airborne. The Epstein-Barr Virus mainly replicates in the beta-lymphocytes and also can replicate in the epithelial cells of the pharynx and parotodid duct. Common symptoms are fever, pharyngitis, adenopathy, malaise, and an atypical lymphocytosis.

Application to Biotechnology

Does this organism produce any useful compounds or enzymes? What are they and how are they used?

In a EBV-negative Burkitt's lympoma-derive cell line, the cellular antiapoptotic bf1-1 gene allows protection from apoptosis in conditions where there is a deficit in growth factor. The latent membrane protein 1 of EBV and CD40 its functional homologue can drive bf1-1. This can happen through NF-B-dependent enhancer elements that are found in the bf1-1 promoter.


(). Here we show that the EBV nuclear antigen 2 (EBNA2) also upregulates bfl-1. EBNA2 trans-activation of bfl-1 requires CBF1 (or RBP-J), a nuclear component of the Notch signaling pathway, and there is an essential role for a core consensus CBF1-binding site on the bfl-1 promoter. trans-activation is dependent on the EBNA2-CBF1 interaction, is modulated by other EBV gene products known to interact with the CBF1 corepressor complex, and does not involve activation of NF-B. bfl-1 expression is induced and maintained at high levels by the EBV growth program in a lymphoblastoid cell line, and withdrawal of either EBNA2 or LMP1 does not lead to a reduction in bfl-1 mRNA levels in this context, whereas the simultaneous loss of both EBV proteins results in a major decrease in bfl-1 expression. These findings are relevant to our understanding of EBV persistence, its role in malignant disease, and the B-cell developmental process.

Current Research

Enter summaries of the most recent research here--at least three required

References

http://www.cdc.gov/ncidod/diseases/ebv.htm National Center For Infectious Diseases "Epstein-Bard Virus and Infectious Mononucleosis."

Andersson JP. Clinical aspects of Epstein-Barr virus infection. Scand J Infect Dis Suppl 1991;80:94-104

Baer R, Bankier AT, Biggin MD, Deininger PL, Farrell PJ, Gibson TJ, Hatfull G, Hudson GS, Satchwell SC, Séguin C, et al. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 310(5974):207–211. [PubMed]

Bailey RE. Diagnosis and treatment of infectious mononucleosis. Am Fam Physician 1994;49:879-88.

http://www.ncbi.nlm.nih.gov/pubmed/8713470 Schmidt CW, Misko IS. "The ecology and pathology of Epstein-Barr virus." Immunol Cell Biol. 1995 Dec;73(6):489-504

http://linkinghub.elsevier.com/retrieve/pii/S1097276502004653 "Structure of the Epstein-Barr Virus gp42 Protein Bound to the MHC Class II Receptor HLA-DR1." Molecular Cell , Volume 9 , Issue 2 , Pages 375 - 385 M . Mullen , K . Haan , R . Longnecker , T . Jardetzky

B. D'Souza, M. Rowe, and D. Walls, J. Virol. 74:6652-6658, 2000

[Sample reference] Takai, K., Sugai, A., Itoh, T., and Horikoshi, K. "Palaeococcus ferrophilus gen. nov., sp. nov., a barophilic, hyperthermophilic archaeon from a deep-sea hydrothermal vent chimney". International Journal of Systematic and Evolutionary Microbiology. 2000. Volume 50. p. 489-500.