LMP2A also has dramatic effects on development and differentiation as evidenced by transgenic mouse phenotypes and analysis of transcriptional profiles. The molecular bases for these functions of LMP2A underlie its contribution to development of various epithelial and lymphoid malignancies including nasopharyngeal carcinoma and Hodgkin's Lymphoma, and help to explain the role of LMP2A in the EBV life cycle and maintenance of viral latency.
EBERs are the most abundant viral transcript produced during latent infection by EBV in a wide variety of cell types and disease conditions. They have been demonstrated to have a variety of effects on cell growth and physiology in experiments performed in vitro and in cell culture remains to be defined. Although the abundance of EBERs in latently infected cells implies an important function, their biological role in vivo and their molecular mechanisms of action remain poorly understood.
The current state of knowledge with respect to the regulation of EBER expression, their structure, their interactions with cellular proteins and their roles in protecting EBV mediated cell transformation is presented and the controversies regarding EBER functions are discussed. Similar to other herpesviruses, EBV exhibits a biphasic life cycle involving a replicative phase and a latency phase.
Following initial infection, EBV preferentially exists in host cells in a state of "latency" in which no viral production occurs. Upon receiving certain activation signals, latency can be disrupted and entry into the productive replicative stage of the life cycle ensues. Following the initial triggering of the lytic cycle, progression of the lytic cascade is manifested by the expression of the viral immediate-early IE and early viral regulatory proteins, Zta, Rta, and Mta.
In this chapter, we will focus on the biological roles of these key EBV lytic cycle regulators and we will discuss the interplay between the lytic and latent phases of the EBV life cycle. Lyme Disease and Relapsing Fever Spirochetes. Climate Change and Microbial Ecology. Help and information Contact. The glycine-alanine domain minimizes translation, binds to proteasomes and inhibits EBNA-1 proteolysis.
EBNA-1 a. The key LMP-1 functional domains are: i six transmembrane domains TM1—6 , which mediate raft association, constitutive aggregation and constitutive signaling; and ii two transformation effector sites TES1 and TES2. LMP-1 oligomerizes on the plasma membrane through TM1 interaction with TM3—6, forming a ligand-independent signaling complex. LMP-2A promotes B-cell growth, 62 induces B lymphoma, has a transformation ability in vitro and in vivo , which was blocked by an immunoreceptor tyrosine-based activation motif LMP-2A mutant, the Syk inhibitor or Syk-specific small interfering RNA, and is important but not essential for in vitro primary B-lymphocyte growth transformation, latent infection and lytic virus replication in vitro 43 , , but is essential for growth transformation of germinal center B cells, which do not express the genuine BCR because of deleterious somatic hypermutations in their immunoglobulin genes; it increases the prosurvival and anti-inflammatory cytokine IL via PI3K, upregulates genes associated with cell cycle induction and inhibition of apoptosis and downregulates genes associated with B-cell-specific factors and immunity similarly to those in HRS cells of HL, and it counteracts the antiproliferative effect of the S10A mutant to promote the S-phase entry.
EBNA-3C functions as a coactivator and corepressor. EBNA-3A represses contiguous clusters arrayed in the human genome by polycomb group-mediated epigenetic silencing. A Bim is a cellular inducer of apoptosis. The expression of chemokine CXCL12 and its receptor contributes to EBV-positive peripheral blood mononuclear cell growth in mice with severe combined immunodeficiency disease.
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This article has been cited by other articles in PMC. Introduction A physican by name Burkitt was the first to describe a unique lymphoma. Table 1 Roles of EBV-encoded latent genes. Open in a separate window.
LMP1 structure, domain and interactions The key LMP-1 functional domains are: i six transmembrane domains TM1—6 , which mediate raft association, constitutive aggregation and constitutive signaling; and ii two transformation effector sites TES1 and TES2.
Figure 1. Notes The authors declare no conflict of interest. Virus particles in cultured lymphoblasts from Burkitt's lymphoma. Immunofluorescence in cells derived from Burkitt's lymphoma. J Bacteriol. Observations on childhood infections with the Epstein—Barr virus. J Infect Dis. Antibodies to Epstein—Barr virus in Burkitt's lymphoma and control groups.
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Rev Med Virol. EBV is found all over the world. Most people get infected with EBV at some point in their lives. EBV spreads most commonly through bodily fluids, primarily saliva. EBV can cause infectious mononucleosis , also called mono, and other illnesses.
Many people become infected with EBV in childhood. EBV infections in children usually do not cause symptoms, or the symptoms are not distinguishable from other mild, brief childhood illnesses. People who get symptoms from EBV infection, usually teenagers or adults, get better in two to four weeks. However, some people may feel fatigued for several weeks or even months. After you get an EBV infection, the virus becomes latent inactive in your body. In some cases, the virus may reactivate.
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