EBV interferes with the sensitivity of Burkitt lymphoma Akata cells to etoposide.
Burkitt lymphoma (BL) commonly exhibits Epstein-Barr virus (EBV) positivity associated with latent chronic infection. Models of acute EBV infection have been associated with cellular resistance to apoptosis. However, the effect of latent long-term EBV infection on apoptosis induced by drugs is not well defined. To determine this, we have studied the response of the Akata EBV+ cell line (type I latency) to etoposide, before and after downregulating EBV gene expression. We observed that downregulating EBV nuclear antigen-1 (EBNA-1) expression with siRNAs reverted cellular sensitivity to etoposide. In accordance with this finding, Akata EBV+ cells showed increased sensitivity to etoposide, when compared to the Akata EBV- cells. We also observed that Akata EBV+ cells presented increased apoptosis levels and decreased Bcl-xL mRNA and protein levels, when compared to the Akata EBV- cells. In addition, Akata EBV+ cells contained less endoplasmic reticulum (ER) than EBV- cells. Finally, downregulation of EBV with EBNA-1 siRNAs caused an increase in the expression of Bcl-xL indicating that EBV is responsible for the differences found between the Akata EBV+ and EBV- cell lines.
Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
Raquel T
RT
Lima
Hugo
H
Seca
Paula
P
Soares
Maria São José
MS
Nascimento
M Helena
MH
Vasconcelos
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D002051:Burkitt Lymphoma / Q000821:virology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology*; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D019309:Epstein-Barr Virus Nuclear Antigens; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014763:Viral Matrix Proteins; D051020:bcl-X Protein; D005047:Etoposide; C417029:EBV-encoded nuclear antigen 1