Flowchart: Preparation: Brlf1
 

 


                  

Text Box: BRLF1                                                    

                                           

                     

         

Estein-Barr Virus                                                          

Text Box: Akt                         

                                                    

                                                            

Virus Genes. 2006 Jun;32(3):327-34.

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Functional Role of Phosphatidylinositol 3-kinase/Akt Pathway on Cell Growth and Lytic Cycle of Epstein-Barr Virus in the Burkitt's Lymphoma Cell Line, P3HR-1.

Mori T, Sairenji T.

Division of Biosignaling, Department of Biomedical Sciences,
School of Life Science, Faculty of Medicine, Tottori University, 86 Nishi-cho, 683-8503, Yonago, Japan, sairen@grape.med.tottori-u.ac.jp.

The phosphatidylinositol 3-kinase (PI3-K)/Akt pathway is involved in various malignancies, but the role of PI3-K/Akt pathway in Epstein-Barr virus (EBV) infected Burkitt's lymphoma (BL) cells remains unclear. To elucidate therapeutic targets for BL, this study investigates the effect of PI3-K/Akt pathway in: EBV-positive BL cell lines Raji, P3HR-1, Akata and Daudi; and EBV-negative BL cell lines Ramos and BJAB. Results of analyses indicate that Akt was constitutively phosphorylated in BJAB, P3HR-1, Akata, and Daudi but not in Ramos and Raji cells. We characterized Akt phosphorylation on cell growth and EBV lytic cycle in P3HR-1 cells, which were phosphorylated most intensively. The Akt was equally phosphorylated in cells cultured with and without fetal bovine serum for a few days. Akt phosphorylation and cell growth were inhibited by PI3-K specific inhibitor LY294002 in a dose-dependent manner. LY294002 markedly down regulated expression of EBV lytic gene BRLF1 protein Rta, BMRF1 protein EA-D, but not BZLF1 protein ZEBRA. The inhibitor reduced viral capsid antigen (VCA) positive cells. Down regulation of Rta by LY294002 occurred at the transcriptional level. These results demonstrate that PI3-K/Akt pathway is activated constitutively in P3HR-1 cells; it promotes cell growth and the lytic cycle cascade downstream of ZEBRA.

PMID: 16732486 [PubMed - in process]