Abstract
Viruses have evolved various mechanisms to evade host immunity and ensure efficient viral replication and persistence. Several DNA tumor viruses modulate host DNA methyltransferases for epigenetic dysregulation of immune-related gene expression in host cells. The host immune responses suppressed by virus-induced aberrant DNA methylation are also frequently involved in antitumor immune responses. Here, we describe viral mechanisms and virus–host interactions by which DNA tumor viruses regulate host DNA methylation to evade antiviral immunity, which may contribute to the generation of an immunosuppressive microenvironment during cancer development. Recent trials of immunotherapies have shown promising results to treat multiple cancers; however, a significant number of non-responders necessitate identifying additional targets for cancer immunotherapies. Thus, understanding immune evasion mechanisms of cancer-causing viruses may provide great insights for reversing immune suppression to prevent and treat associated cancers.
Highlights
Recent studies have revealed that DNA methylation is associated with many different diseases including microbial infections and cancers
We summarize host genes with diverse functions regulated by DNA methylation in cancers associated with DNA tumor viruses in DNA methylation-associated pathogenesis for EBV-associated gastric carcinoma (EBVaGC) [70] and hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) [79,80] have been previously reviewed in detail
LMP1 effects on DNMT1 levels in lymphoblastoid cells compared to EBVaGC and nasopharyngeal carcinoma (NPC) could be due to differing EBV latency stages, which are dictated by distinct EBV gene expression patterns
Summary
Recent studies have revealed that DNA methylation is associated with many different diseases including microbial infections and cancers (reviewed in [1,2]). Our study has shown that the prevalence of CpG dinucleotides, the target motif of DNA methylation, is significantly lower in the genomes of papillomaviruses compared to other dinucleotide motifs [45] These results suggest that gene expression regulation by DNA methylation may play a critical role in arms races between viruses and their hosts. To evade detection and restriction by the host immune response, viruses employ various mechanisms to control gene expression related to immunity, including hijacking epigenetic machinery (reviewed in [46,47]). We discuss several compelling studies showing that DNA tumor virus regulation of host immune-related genes by DNA methylation contributes to cancer progression and is likely a result of virus-driven immune suppression to evade host antiviral responses. 2018, 10, and is likely a result of virus-driven immune suppression to evade host antiviral responses
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