CADM1 is essential for KSHV-encoded vGPCR-and vFLIP-mediated chronic NF-κB activation

• DOI: 10.1371/journal.ppat.1006968
• Publication Date: 2018-04-26T17:26:42Z
• Authors: Richard Hunte; Patricia Alonso; Remy Thomas; Cassandra Alexand...; Juan Carlos Ramos; Louise van der We...; Juan Dominguez-Be...; Wasif Noor Khan; Noula Shembade
• Keywords: Primary effusion lymphoma; Lytic cycle; Kaposi's sarcoma-associated herpesvirus; IκB kinase

Approximately 12% of all human cancers worldwide are caused by infections with oncogenic viruses. Kaposi's sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8) is one the viruses responsible for cancers, including Kaposi’s (KS), Primary Effusion Lymphoma (PEL), and lymphoproliferative disorder multicentric Castleman’s disease (MCD). Chronic inflammation mediated KSHV infection plays a decisive role in development survival these cancers. NF-κB, family transcription factors regulating inflammation, cell survival, proliferation, persistently activated KSHV-infected cells. The latent lytic expressing oncogenes involved NF-κB activation vFLIP/K13 vGPCR, respectively. However, mechanisms which vFLIP vGPCR poorly understood. In this study, we have found that host molecule, Cell Adhesion Molecule 1 (CADM1), robustly upregulated PBMCs KSHV-associated PEL Further investigation determined both interacted CADM1. PDZ binding motif localized at carboxyl terminus CADM1 essential to maintain chronic activation. Membrane lipid raft associated interaction critical initiation IKK kinase complex addition, played roles These data indicate key pathways during phases life cycle