Implication of human herpesviruses in oncogenesis through immune evasion and supression

Abstract

All human herpesviruses (HHVs) have been implicated in immune system evasion and suppression. Moreover, two HHV family members, i.e. EBV and KSHV, are recognised as oncogenic viruses. Our literature review summarises additional examples of possible oncogenic mechanisms that have been attributed to other HHVs. In general, HHVs affect almost every cancer-implicated branch of the immune system, namely tumour-promoting inflammation, immune evasion, and immunosuppression. Some HHVs accomplish these effects by inhibiting apoptotic pathways and by promoting proliferation. Mechanisms related to immunosupression and low grade chronic inflammation could eventually result in the initiation and progression of cancer. In this article we open a discussion on the members of Herpesviridae, their immune evasion and suppression mechanisms, and their possible role in cancer development. We conclude that discerning the mechanisms of interplay between HHV, immune system, and cancer is essential for the development of novel preventative and therapeutic approaches for cancer treatment and prophylaxis.

Constitutive Activation of Interleukin-13/STAT6 Contributes to Kaposi's Sarcoma-Associated Herpesvirus-Related Primary Effusion Lymphoma Cell Proliferation and Survival

“…It has been reported that constitutive activation of STAT6 is widely associated with tumor development, including virus-associated cancers (13,15,16,33,34). KSHV, a recently discovered oncogenic herpesvirus, has been shown to escape host immune surveillance through modulating the JAK-STAT pathway (35,36). However, the specific molecular mechanism through which signal pathway modulation occurs remains largely uncharacterized.…”

Identification of Kaposi Sarcoma Herpesvirus (KSHV) vIRF1 Protein as a Novel Interaction Partner of Human Deubiquitinase USP7

“…In the latent state, herpesviruses express only a small number of proteins essential for suppressing the host immune system (2). HHVs have evolved various mechanisms for host immune evasion including inhibition of cellular senescence and apoptosis as well as promoting cell proliferation (3). Another strategy to evade host immune surveillance is through expression of viral homologues of genes that are the host's first line of defense against viral infection such as interferons and interferon regulatory factors (IRFs) and therefore sabotage the function and regulation of the cellular proteins (4).…”

“…Another strategy to evade host immune surveillance is through expression of viral homologues of genes that are the host's first line of defense against viral infection such as interferons and interferon regulatory factors (IRFs) and therefore sabotage the function and regulation of the cellular proteins (4). Deregulation of cellular proteins involved in growth control by HHVs has led to recognition of some HHVs as underlying agents of cancer (3,5).…”

Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Inhibits Major Histocompatibility Complex Class II Expression by Disrupting Enhanceosome Assembly through Binding with the Regulatory Factor X Complex

“…One of the main factors contributing to the successful lifelong persistence of KSHV is its astounding ability to hide from host immune surveillance. During the course of evolution, KSHV has evolved multiple mechanisms to evade and modulate nearly all aspects of both the innate and adaptive immunities of infected hosts (5)(6)(7).…”