Reaktion des Epstein-Barr-Virus und seiner Wirtszelle B95-8 auf die Überexpression der extrazellulär-regulierten Kinase 3 (p97)

The activation of the Epstein-Barr virus (EBV) lytic cycle is of significant importance for the viral pathogenesis. Until now the molecular mechanisms resulting in EBV-reactivation under physiological conditions are not fully understood.It is known that stimulation of the EBV genome-positive Burkitt-lymphome cell line Raji with the ganglioside IV3NeuAcnLc4 leads to induction of growth-inhibition, cell differentiation processes and activation of the viral lytic cycle. 35 genes were identified to be transciptionally induced in response to ganglioside treatment. One of them encodes the MAP-kinase ERK3 (p97).The goal of this thesis was to examine the effects of ERK3 (p97)-overexpression in cells of the EBV-genome-positive cell line B95-8 on the activation of the viral lytic cycle and on cellular proliferation.Transfection of B95-8 cells with an ERK3 (p97)-overexpression vector lead to ERK3 (p97) overexpression on transcript level.ERK3 (p97) overexpression was followed by the overexpression of the immediate early gene BRLF1 and of Early Antigen (EA-D), the gene product of the delayed early gene BMRF1. Thus, an ERK3 (p97) triggered induction of the viral lytic cycle was proven.ERK3 (p97) overexpression did not influence the rate of DNA-synthesis or cellular division in B95-8 cells. The expression of the surface antigens CD 44, CD 11a, CD23, CD 54, CD 30, CD19, CD 58, CD 40 remained unchanged.Overexpression of the genes coding for 14-3-3zeta/PLA2, protein kinase B (PKB) and s-adenosylhomocystic hydrolase (SAH) induced a significant ERK3 (p97) overexpression in B95-8 cells.Previous experiments had shown viral reactivation in response to overexpression of the gene products mentioned above. Thus, a role for ERK3 (p97) in 14-3-3zeta/PLA2-, PKB-, and SAH- triggered reactivation of the viral lytic cycle can be assumed.The elucidation of the molecular mechanisms leading to lytic EBV-reactivation could be the basis of further therapeutic options. The induction of ERK3 (p97) in EBV-genome positive tumors leading to activation of the viral lytic cycle might initiate self-destruction of tumor tissue or might allow destruction of the tumor cells throughout virostatic treatment.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2006

Author dc:creator

• Kaufmann, Anne Caroline

Contributors dc:contributor

• Ritter, Klaus

• info:eu-repo/classification/ddc/610
• Medizin
• Epstein-Barr-Virus
• Proteinkinase B
• Phospholipase A2
• ERK 3 (p97)
• BZLF1
• BRLF1
• S-Adenosylhomocystein Hydrolase
• Early-Antigen (EA-D)
• s-adenosylhomocystic hydrolase

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-122934%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:61257