The interplay between EBV and KSHV viral products and NF-κB pathway in oncogenesis

Abstract

Among the DNA tumor viruses Epstein-Barr virus (EBV) and Kaposi sarcoma herpesvirus (KSHV), account for a considerable percentage of virus-associated cancers. Deregulation of transcription factors signaling pathways is one of the most significant oncogenic characteristics of EBV and KSHV. NF-κB is a transcription factor that play a remarkable role in oncogenesis because of its function as a master regulator of a spectrum of genes involved in physiological and pathophysiological process. Constitutive activation of NF-κB is a frequent and well-described event in many human malignancies. Compelling evidence represent EBV and KSHV are capable of targeting different components of NF-κB cascade. Here, we summarized recent findings to clarify the precise relationship between dysregulation of NF-κB and EBV and KSHV-related malignancies. This essay also emphasizes on contribution of various viral products in developing cancer through alteration of NF-κB signaling pathway.

Keywords: EBV; KSHV; NF-κB; Neoplasm.

Fig. 1

an overview of virus-deregulated NF-κB signaling pathway in oncogenesis. Viral products target different components of NF-κB cascade in order to induce dimers activation (p65,p50 and p52,RELB; other dimers are not shown), driving the transcription of NF-κB target genes following the nuclear translocation. The stimulated genes products can be involved in inflammation, cell growth and cell survival, angiogenesis, metastasis, ect. On the other hand, the NF-κB may lead to production of the factors which negatively regulate the cascade such as IκBα. However, virus might be able to overcome it. For example, KSHV encodes mir-K1 mir-k12–1 to suppress IκBα. Infm/Cyto; inflammation/cytokine, Gth/Serv/Prol/Imotz; growth/survival/proliferation/immortalization

Fig. 2

EBV-deregulated NF-κB signaling pathway in oncogenesis. Viral products serve different strategies to activate NF-κB cascade. However, some may induce opposite effect. EAL; EBV-associated lymphomas, Lyt; lytic, Lat; latent

Fig. 3

KSHV-deregulated NF-κB signaling pathway in oncogenesis. *Constitutive activation; Transient or low activation of NF-κB results in KSHV lytic replication, whereas constitutive activation of NF-κB may leads to KSHV latency. Virus is capable of engaging signaling molecules in NF-κB activation process. MLT; MALT1, CLS; capillary-like structures, Lat; latent, Lyt/reA; lytic/reactivation