Global cancer incidence and mortality are on the rise. Although cancer is fundamentally a non-communicable disease, a large number of cancers are known to have a viral aetiology. A high burden of infectious agents (Human immunodeficiency virus (HIV), human papillomavirus (HPV), hepatitis B virus (HBV)) in certain Sub-Saharan African countries drives the rates of certain cancers. About one-third of all cancers in Africa are attributed to infection. Seven viruses have been identified with carcinogenic characteristics, namely the HPV, HBV, Hepatitis C virus (HCV), Epstein–Barr virus (EBV), Human T cell leukaemia virus 1 (HTLV-1), Kaposi’s Sarcoma Herpesvirus (KSHV), and HIV-1. The cellular splicing machinery is compromised upon infection, and the virus generates splicing variants that promote cell proliferation, suppress signalling pathways, inhibition of tumour suppressors, alter gene expression through epigenetic modification, and mechanisms to evade an immune response, promoting carcinogenesis. A number of these splice variants are specific to virally-induced cancers. Elucidating mechanisms underlying how the virus utilises these splice variants to maintain its latent and lytic phase will provide insights into novel targets for drug discovery. This review will focus on the splicing genomics, epigenetic modifications induced by and current therapeutic strategies against HPV, HBV, HCV, EBV, HTLV-1, KSHV and HIV-1.

中文翻译：

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病毒肿瘤基因组学中的异常剪接事件和表观遗传学：当前的治疗策略

全球癌症发病率和死亡率呈上升趋势。尽管癌症从根本上说是一种非传染性疾病，但已知大量癌症具有病毒病因。在某些撒哈拉以南非洲国家，传染源（人类免疫缺陷病毒 (HIV)、人乳头瘤病毒 (HPV)、乙型肝炎病毒 (HBV)）的高负担推动了某些癌症的发病率。非洲约有三分之一的癌症归因于感染。七种病毒已被确定具有致癌特征，即 HPV、HBV、丙型肝炎病毒 (HCV)、爱泼斯坦-巴尔病毒 (EBV)、人类 T 细胞白血病病毒 1 (HTLV-1)、卡波西肉瘤疱疹病毒 (KSHV) 和HIV-1。细胞剪接机制在感染时受到损害，病毒产生剪接变体，促进细胞增殖，抑制信号通路，抑制肿瘤抑制因子，通过表观遗传修饰改变基因表达，以及逃避免疫反应的机制，促进致癌作用。许多这些剪接变体对病毒诱导的癌症具有特异性。阐明病毒如何利用这些剪接变体来维持其潜伏期和裂解期的潜在机制将为药物发现的新目标提供见解。本综述将重点关注剪接基因组学、由 HPV、HBV、HCV、EBV、HTLV-1、KSHV 和 HIV-1 诱导的表观遗传修饰和当前的治疗策略。阐明病毒如何利用这些剪接变体来维持其潜伏期和裂解期的潜在机制将为药物发现的新目标提供见解。本综述将重点关注剪接基因组学、由 HPV、HBV、HCV、EBV、HTLV-1、KSHV 和 HIV-1 诱导的表观遗传修饰和当前的治疗策略。阐明病毒如何利用这些剪接变体来维持其潜伏期和裂解期的潜在机制将为药物发现的新目标提供见解。本综述将重点关注剪接基因组学、由 HPV、HBV、HCV、EBV、HTLV-1、KSHV 和 HIV-1 诱导的表观遗传修饰和当前的治疗策略。