Modulation of apoptosis by human papillomavirus (HPV) oncoproteins

Abstract

The regulation of host-mediated apoptosis by the E6 and E7 oncoproteins has garnered attention because it is believed to be an important strategy employed by high-risk (HR)-human papillomaviruses (HPVs) to evade immune surveillance. Additionally, the revelation that E5 can protect cells from tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis suggests that it may also play a role in undermining host defense mechanisms. Cellular transformation is an unintended consequence of persistent infection by HR-HPVs, and it is therefore likely that the primary function of E5, E6 and E7 is to regulate cell survival throughout the normal viral life cycle in order to ensure viral replication and promote the spread of progeny. The purpose of this article is to review the literature on the regulation of host-mediated apoptosis by E5, E6 and E7 that describes the mechanisms employed by HR-HPVs to persist in the host and create the conditions necessary for cellular transformation.

Human Papillomavirus Type 16 E5 Protein Induces Expression of Beta Interferon through Interferon Regulatory Factor 1 in Human Keratinocytes

“…HPV16 E5 is a hydrophobic protein of 83 amino acids that associates with the Golgi apparatus, the endoplasmic reticulum, and nuclear membrane (17). E5 exhibits transforming activity (52) and cooperates with E6 and E7 to induce a malignant phe-notype (6,51,56).…”

The Interaction between Human Papillomavirus Type 16 and FADD Is Mediated by a Novel E6 Binding Domain

“…In addition, while some viruses have developed mechanisms to evade the host immune system by producing homologues of cytokines and chemokines, as well as their receptors (1,6,14), others have developed means to obstruct both the extrinsic and intrinsic cell death pathways simultaneously (9,53,62). In order to escape elimination by the host, the HPV modulates apoptosis through several mechanisms (26), including the interaction of its oncoprotein E6 with the tumor suppressor protein p53 (46,64). In addition, E6 can also bind to TNFR1 (63), FADD (21), procaspase 8 (31), bax (35,40), and bak (17,56), thus preventing proapoptotic signal transduction.…”

Human Papillomaviruses Oncoproteins

“…Viral oncogenes are essential for carcinogenesis and their expression induces the tumorigenic state which ensures cell survival, essential for viral replication and the spread of progeny [31] Although the viral oncogenes were intensively studied, new data bring more information about their involvement in cervix carcinogenesis.…”