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.