EBV can protect latently infected B cell lymphomas from death receptor-induced apoptosis.
The relationship between EBV infection and sensitivity to death receptor (DR)-induced apoptosis is poorly understood. Using EBV- and EBV+ BJAB cells, we provide the first evidence that EBV can protect latently infected B cell lymphomas from apoptosis triggered through Fas or TRAIL receptors. Caspase 8 activation was impaired and cellular FLIP recruitment was enriched in death-inducing signaling complexes formed in EBV-infected BJAB cells relative to parent BJAB cells. Furthermore, latent membrane protein 1 expression alone could reduce caspase activation and confer partial resistance to DR apoptosis in BJAB cells. This protective effect was dependent on C-terminal activating region 2-driven NF-kappaB activation, which in turn up-regulated cellular FLIP expression in latent membrane protein 1+ BJAB cells. Thus, the ability of latent EBV to block DR apoptosis may help to ensure the survival of host cells during B cell differentiation, and contribute to the development of B cell lymphomas, especially in immunocompromised individuals.
Snow
Andrew L
AL
Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lambert
Stacie L
SL
Natkunam
Yasodha
Y
Esquivel
Carlos O
CO
Krams
Sheri M
SM
Martinez
Olivia M
OM
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D020740:Chimerin Proteins / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D053222:Fas Ligand Protein; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048069:Tumor Necrosis Factors / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D020740:Chimerin Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D014763:Viral Matrix Proteins; D020169:Caspases