Role of Virus-Induced Host Cell Epigenetic Changes in Cancer

Abstract

The tumor viruses human T-lymphotropic virus 1 (HTLV-1), hepatitis C virus (HCV), Merkel cell polyomavirus (MCPyV), high-risk human papillomaviruses (HR-HPVs), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpes virus (KSHV) and hepatitis B virus (HBV) account for approximately 15% of all human cancers. Although the oncoproteins of these tumor viruses display no sequence similarity to one another, they use the same mechanisms to convey cancer hallmarks on the infected cell. Perturbed gene expression is one of the underlying mechanisms to induce cancer hallmarks. Epigenetic processes, including DNA methylation, histone modification and chromatin remodeling, microRNA, long noncoding RNA, and circular RNA affect gene expression without introducing changes in the DNA sequence. Increasing evidence demonstrates that oncoviruses cause epigenetic modifications, which play a pivotal role in carcinogenesis. In this review, recent advances in the role of host cell epigenetic changes in virus-induced cancers are summarized.

Cell-Cell Fusion Mediated by Viruses and HERV-Derived Fusogens in Cancer Initiation and Progression

“…In addition to HPV, further oncogenic viruses could induce bi-and multinucleation, such as Hepatitis B and C virus, Epstein-Barr virus, Kaposi sarcoma virus and Human T-lymphotropic virus 1 (for review see [21,206,219]). However, bi-nucleation and polyploidy (and aneuploidy/GCIN) is rather induced due to a persistent expression of viral oncoproteins that leads to a dysregulation of several important cellular processes and not via cell-cell fusion [206,219]. Thus, viral oncoproteins could activate survival pathways, initiate DNA synthesis and cell cycle progression, activate proto-oncogenes, inactivate tumor suppressors and cause epigenetic modifications [206,219].…”

“…However, bi-nucleation and polyploidy (and aneuploidy/GCIN) is rather induced due to a persistent expression of viral oncoproteins that leads to a dysregulation of several important cellular processes and not via cell-cell fusion [206,219]. Thus, viral oncoproteins could activate survival pathways, initiate DNA synthesis and cell cycle progression, activate proto-oncogenes, inactivate tumor suppressors and cause epigenetic modifications [206,219]. Each of these mechanisms alone or in combination could sufficiently cause replication errors, chromosome missegregation and mitotic errors, eventually leading to aneuploid and multinucleated cells including PGCCs.…”

“…The merging of two plasma membranes is a multi-step process of various proteins and fusogens that have been identified as indispensable mediators of cell-cell fusion to overcome plasma membrane merging-associated energetic barriers [3][4][5][6][7][8]19,20,89]. Enveloped and some non-enveloped viruses could induce syncytia/MNGC formation due to the expression of evolutionarily optimized fusogens [50,51,[121][122][123] whereby oncogenic viruses could lead to PGCC formation [21,206,219]. About 8% of the human genome is of retroviral origin [136][137][138][139] and transcripts including env proteins have been identified in normal and tumorigenic tissues with fusogenic properties [138,139,145]).…”

Engineering Macrophages via Nanotechnology and Genetic Manipulation for Cancer Therapy

“…Tumor growth is often accompanied by a certain degree of inflammation, and the underlying mechanisms are complex ( 11 , 12 ). For example, chronic viral infection induces constant inflammation and contributes to the development of some types of cancer ( 55 , 56 ). In addition, tumor blood vessels are often distributed abnormally and have a broken structure, and they cannot meet the oxygen and nutrition requirements of fast-growing tumor cells, resulting in hypoxia and nutrition deficiency within some tumor areas.…”

Functional Domains of the Early Proteins and Experimental and Epidemiological Studies Suggest a Role for the Novel Human Polyomaviruses in Cancer

“…(Baylin and Jones, 2016;Zhang et al, 2020)]. All human tumor viruses can trigger epigenetic changes in the host cell (Pietropaolo et al, 2021). SV40, BKPyV, JCPyV and MCPyV were found to provoke epigenetic changes (Balakrishnan and Milavetz, 2017;Pietropaolo et al, 2021).…”