Kaposi's sarcoma-associated herpesvirus oncoprotein K13 protects against B cell receptor induced growth arrest and apoptosis through NF-κB activation

Graham, Ciaren and Matta, Hittu and Yang, Yanqiang and Yi, Han and Suo, Yulan and Tolani, Bhairavi and Chaudhary, Preet M. (2013) Kaposi's sarcoma-associated herpesvirus oncoprotein K13 protects against B cell receptor induced growth arrest and apoptosis through NF-κB activation. Journal of Virology, 87 (4). pp. 2242-2252. ISSN 0022-538x

Full content URL: http://dx.doi.org/10.1128/JVI.01393-12

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Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) has been linked to the development of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease (MCD). We have characterized the role of KSHV-encoded viral FLICE inhibitory protein K13 in the modulation of anti-IgM induced growth arrest and apoptosis in B cells. We demonstrate that K13 protects WEHI 231, an immature B cell line, against anti-IgM induced growth arrest and apoptosis. The protective effect of K13 was associated with the activation of the NF-κB pathway and was deficient in its mutant, K13-58AAA, and a structural homolog, vFLIP E8, which lack NF-κB activity. K13 upregulated the expression of NF-κB subunit RelB and blocked the anti-IgM induced decline in c-Myc and rise in p27(Kip1) that have been associated with growth arrest and apoptosis. K13 also upregulated the expression of Mcl-1, an anti-apoptotic member of the Bcl2 family. Finally, K13 protected the mature B cell line Ramos against anti-IgM induced apoptosis through NF-κB activation. Inhibition of anti-IgM induced apoptosis by K13 may contribute to the development of KSHV-associated lymphoproliferative disorders.

Additional Information:Published ahead of print 12 December 2012
Keywords:KSHV, K13, vFLIP, Mutlicentric Castleman Disease, Apoptosis, BCR
Subjects:C Biological Sciences > C550 Immunology
C Biological Sciences > C540 Virology
Divisions:College of Science > School of Life Sciences
ID Code:7319
Deposited On:21 Jan 2013 12:30

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