RETRACTED: KSHV vFLIP is essential for the survival of infected lymphoma cells (Retracted Article)

被引:241
作者
Guasparri, I [1 ]
Keller, SA [1 ]
Cesarman, E [1 ]
机构
[1] Cornell Univ, Dept Pathol, Weill Med Coll, New York, NY 10021 USA
关键词
HHV-8; NF-kB; Kaposi's sarcoma; AIDS; viral oncogenes;
D O I
10.1084/jem.20031467
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Primary effusion lymphomas (PELs) associated with infection by the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) have constitutive nuclear factor (NF)-kappaB activity that is essential for their survival, but the source of this activity is unknown. We report that viral FADD-like interleukin-1-beta-converting enzyme [FLICE/caspase 8]-inhibitory protein (FLIP) activates NF-kappaB more potently than cellular FLIP in B cells and that it is largely responsible for NF-kappaB activation in latently infected PEL cells. Elimination of vFLIP production in PEL cells by RNA interference results in significantly decreased NF-kappaB activity, down-regulation of essential NF-kappaB-regulated cellular prosurvival factors, induction of apoptosis, and enhanced sensitivity to external apoptotic stimuli. vFLIP is the first virally encoded gene shown to be essential for the survival of naturally infected tumor cells.
引用
收藏
页码:993 / 1003
页数:11
相关论文
共 36 条
[1]   Kaposi's sarcoma-associated herpesvirus encoded vFLIP induces cellular IL-6 expression:: the role of the NF-κB and JNK/AP1 pathways [J].
An, JB ;
Sun, YP ;
Sun, R ;
Rettig, MB .
ONCOGENE, 2003, 22 (22) :3371-3385
[2]   Establishment and characterization of a primary effusion (body cavity-based) lymphoma cell line (BC-3) harboring Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in the absence of Epstein-Barr virus [J].
Arvanitakis, L ;
Mesri, EA ;
Nador, RG ;
Said, JW ;
Asch, AS ;
Knowles, DM ;
Cesarman, E .
BLOOD, 1996, 88 (07) :2648-2654
[3]  
Bélanger C, 2001, J HUMAN VIROL, V4, P62
[4]   The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor has broad signaling effects in primary effusion lymphoma cells [J].
Cannon, M ;
Philpott, NJ ;
Cesarman, E .
JOURNAL OF VIROLOGY, 2003, 77 (01) :57-67
[5]   IN-VITRO ESTABLISHMENT AND CHARACTERIZATION OF 2 ACQUIRED IMMUNODEFICIENCY SYNDROME-RELATED LYMPHOMA CELL-LINES (BC-1 AND BC-2) CONTAINING KAPOSIS SARCOMA-ASSOCIATED HERPESVIRUS-LIKE (KSHV) DNA-SEQUENCES [J].
CESARMAN, E ;
MOORE, PS ;
RAO, PH ;
INGHIRAMI, G ;
KNOWLES, DM ;
CHANG, Y .
BLOOD, 1995, 86 (07) :2708-2714
[6]   KAPOSIS SARCOMA-ASSOCIATED HERPESVIRUS-LIKE DNA-SEQUENCES IN AIDS-RELATED BODY-CAVITY-BASED LYMPHOMAS [J].
CESARMAN, E ;
CHANG, Y ;
MOORE, PS ;
SAID, JW ;
KNOWLES, DM .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (18) :1186-1191
[7]   Modulation of the NF-κB pathway by virally encoded death effector domains-containing proteins [J].
Chaudhary, PM ;
Jasmin, A ;
Eby, MT ;
Hood, L .
ONCOGENE, 1999, 18 (42) :5738-5746
[8]   The inhibitor of death receptor signaling, FLICE-inhibitory protein defines a new class of tumor progression factors [J].
Djerbi, M ;
Screpanti, V ;
Catrina, AI ;
Bogen, B ;
Biberfeld, P ;
Grandien, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (07) :1025-1031
[9]   Lymphoma cell lines:: in vitro models for the study of HHV-8+ primary effusion lymphomas (body cavity-based lymphomas) [J].
Drexler, HG ;
Uphoff, CC ;
Gaidano, G ;
Carbone, A .
LEUKEMIA, 1998, 12 (10) :1507-1517
[10]   HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive plasmablastic lymphoma [J].
Dupin, N ;
Diss, TL ;
Kellam, P ;
Tulliez, M ;
Du, MQ ;
Sicard, D ;
Weiss, RA ;
Isaacson, PG ;
Boshoff, C .
BLOOD, 2000, 95 (04) :1406-1412