Singh Rajnish Kumar, Vangala Ramakrishna, Torne Atharva S, Bose Dipayan, Robertson Erle S
Departments of Otorhinolaryngology-Head and Neck Surgery and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Front Microbiol. 2025 Jan 7;15:1484455. doi: 10.3389/fmicb.2024.1484455. eCollection 2024.
Oncogenic gamma herpesviruses, including Epstein-Barr Virus (EBV) and Kaposi's Sarcoma-associated Herpesvirus (KSHV), are opportunistic cancer-causing viruses and induces oncogenesis through complex mechanisms, which involves manipulation of cellular physiology as well as epigenetic and epitranscriptomic reprogramming. In this review, we describe the intricate processes by which these viruses interact with the epigenetic machinery, leading to alterations in DNA methylation, histone modifications, and the involvement of non-coding RNAs. The key viral proteins such as EBNA1 and LMP1 encoded by EBV; LANA and vGPCR encoded by KSHV; play pivotal roles in these modifications by interacting with host factors, and dysregulating signaling pathways. The resultant reprogramming can lead to activation of oncogenes, silencing of tumor suppressor genes, and evasion of the immune response, which ultimately contributes to the oncogenic potential of these viruses. Furthermore, in this review, we explore current therapeutic strategies targeting these epigenetic alterations and discuss future directions for research and treatment. Through this comprehensive examination of the epigenetic and epitranscriptomic reprogramming mechanisms employed by oncogenic gamma herpesviruses, we aim to provide valuable insights into potential avenues for novel therapeutic interventions.
致癌性γ疱疹病毒，包括爱泼斯坦-巴尔病毒（EBV）和卡波西肉瘤相关疱疹病毒（KSHV），是机会性致癌病毒，通过复杂机制诱导肿瘤发生，这涉及对细胞生理学以及表观遗传和表观转录组重编程的操控。在本综述中，我们描述了这些病毒与表观遗传机制相互作用的复杂过程，这些过程导致DNA甲基化、组蛋白修饰的改变以及非编码RNA的参与。由EBV编码的关键病毒蛋白，如EBNA1和LMP1；由KSHV编码的LANA和vGPCR；通过与宿主因子相互作用并失调信号通路，在这些修饰中发挥关键作用。由此产生的重编程可导致癌基因激活、肿瘤抑制基因沉默以及免疫反应逃避，这最终促成了这些病毒的致癌潜力。此外，在本综述中，我们探讨了针对这些表观遗传改变的当前治疗策略，并讨论了未来的研究和治疗方向。通过对致癌性γ疱疹病毒所采用的表观遗传和表观转录组重编程机制进行全面研究，我们旨在为新型治疗干预的潜在途径提供有价值的见解。
