Lovšin Nika, Gangupam Bhavani, Bergant Marušič Martina
Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
Laboratory for Environmental and Life Sciences, University of Nova Gorica, Vipavska 13, 5000 Nova Gorica, Slovenia.
Pathogens. 2024 Feb 20;13(3):187. doi: 10.3390/pathogens13030187.
APOBEC3 proteins are cytidine deaminases that play a crucial role in the innate immune response against viruses, including DNA viruses. Their main mechanism for restricting viral replication is the deamination of cytosine to uracil in viral DNA during replication. This process leads to hypermutation of the viral genome, resulting in loss of viral fitness and, in many cases, inactivation of the virus. APOBEC3 proteins inhibit the replication of a number of DNA tumour viruses, including herpesviruses, papillomaviruses and hepadnaviruses. Different APOBEC3s restrict the replication of different virus families in different ways and this restriction is not limited to one APOBEC3. Infection with DNA viruses often leads to the development and progression of cancer. APOBEC3 mutational signatures have been detected in various cancers, indicating the importance of APOBEC3s in carcinogenesis. Inhibition of DNA viruses by APOBEC3 proteins appears to play a dual role in this process. On the one hand, it is an essential component of the innate immune response to viral infections, and, on the other hand, it contributes to the pathogenesis of persistent viral infections and the progression of cancer. The current review examines the complex interplay between APOBEC3 proteins and DNA viruses and sheds light on the mechanisms of action, viral countermeasures and the impact on carcinogenesis. Deciphering the current issues in the interaction of APOBEC/DNA viruses should enable the development of new targeted cancer therapies.
载脂蛋白B mRNA编辑酶催化多肽样蛋白3（APOBEC3）家族蛋白是胞嘧啶脱氨酶，在包括DNA病毒在内的针对病毒的先天免疫反应中发挥关键作用。它们限制病毒复制的主要机制是在复制过程中将病毒DNA中的胞嘧啶脱氨为尿嘧啶。这一过程导致病毒基因组的超突变，导致病毒适应性丧失，并且在许多情况下使病毒失活。APOBEC3蛋白抑制多种DNA肿瘤病毒的复制，包括疱疹病毒、乳头瘤病毒和嗜肝DNA病毒。不同的APOBEC3以不同方式限制不同病毒家族的复制，并且这种限制不限于一种APOBEC3。DNA病毒感染通常导致癌症的发生和发展。在各种癌症中已检测到APOBEC3突变特征，表明APOBEC3在致癌过程中的重要性。APOBEC3蛋白对DNA病毒的抑制在这一过程中似乎发挥双重作用。一方面，它是对病毒感染的先天免疫反应的重要组成部分，另一方面，它有助于持续性病毒感染的发病机制和癌症的进展。本综述探讨了APOBEC3蛋白与DNA病毒之间的复杂相互作用，并阐明了其作用机制、病毒对策以及对致癌作用的影响。解读APOBEC/DNA病毒相互作用中的当前问题应有助于开发新的靶向癌症治疗方法。
