Kaposi’s sarcoma herpesvirus oncoprotein vFLIP K13 is a potent activator of NF-B and plays a key role in viral pathogenesis. K13 contains a putative TRAF-interacting motif which is reportedly required for its interaction with TRAF2. The K13-TRAF2 interaction is believed to be essential for the recruitment of K13 to the I-kappaB kinase (IKK) complex and for K13-induced NF-B and JNK activation. In addition, TRAF3 has been reported to be required for K13-induced NF-B and JNK activation. We have re-examined the role of the TRAFs in K13 signaling and report that mutations in the putative TRAF-interacting motif of K13 have no deleterious effect on its ability to interact with the IKK complex or activation of the NF-B pathway. Furthermore, endogenously expressed TRAF2 and TRAF3 do not interact with K13 and play no role in K13-induced NF-B activation or its interaction with the IKK complex. Finally, K13 does not activate the JNK pathway. Our results support a model in which K13 bypasses the upstream components of Tumor Necrosis Factor Receptor signaling pathway and directly interacts with the IKK complex to selectively activate the NF-B pathway without affecting the JNK pathway. Selective NF-B activation by K13 might represent a novel strategy employed by the virus to promote latency.