Human herpesvirus 8 viral FLICE-inhibitory protein (vFLIP)

Human herpesvirus 8 viral FLICE-inhibitory protein (vFLIP), encoded by the ORF71 gene of Kaposi's sarcoma-associated herpesvirus (KSHV), is a critical multifunctional protein that promotes viral persistence and oncogenesis. It contains two death effector domains (DEDs) which allow it to inhibit apoptosis by preventing the recruitment and activation of pro-caspase 8 at the death-inducing signaling complex (DISC) (Source: UniProt P0C6L5; PubMed: 15123651). Beyond its anti-apoptotic role, vFLIP is a potent activator of the NF-kappaB pathway through its direct interaction with the IKK-gamma (NEMO) subunit of the IkappaB kinase complex, leading to the constitutive expression of pro-survival and pro-inflammatory genes (Source: PubMed: 22438544). This activity is essential for the survival of HHV-8-infected cells in malignancies such as Kaposi's sarcoma and Primary Effusion Lymphoma (Source: PubMed: 19074281). As a therapeutic target, research focuses on developing small molecules or peptidomimetics that disrupt the vFLIP-IKK interaction to induce apoptosis specifically in latently infected tumor cells (Source: PubMed: 25139309).

Other names

K13ORF71Viral FLICE-inhibitory proteinKSHV vFLIPHHV8-vFLIP

Inhibition of pro-caspase 8 activation and constitutive activation of the IKK complex to trigger NF-kappaB-mediated pro-survival gene expression.