de Andrade Kívia Queiroz, Cirne-Santos Claudio Cesar
Laboratory of Immunology of Infectious Disease, Immunology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, SP, Brazil.
Laboratory of Molecular Virology and Marine Biotechnology, Department of Cellular and Molecular Biology, Institute of Biology, Federal Fluminense University, Niterói 24020-150, RJ, Brazil.
Pathogens. 2023 Dec 17;12(12):1461. doi: 10.3390/pathogens12121461.
The CCCH-type zinc finger antiviral protein (ZAP) in humans, specifically isoforms ZAP-L and ZAP-S, is a crucial component of the cell's intrinsic immune response. ZAP acts as a post-transcriptional RNA restriction factor, exhibiting its activity during infections caused by retroviruses and alphaviruses. Its function involves binding to CpG (cytosine-phosphate-guanine) dinucleotide sequences present in viral RNA, thereby directing it towards degradation. Since vertebrate cells have a suppressed frequency of CpG dinucleotides, ZAP is capable of distinguishing foreign genetic elements. The expression of ZAP leads to the reduction of viral replication and impedes the assembly of new virus particles. However, the specific mechanisms underlying these effects have yet to be fully understood. Several questions regarding ZAP's mechanism of action remain unanswered, including the impact of CpG dinucleotide quantity on ZAP's activity, whether this sequence is solely required for the binding between ZAP and viral RNA, and whether the recruitment of cofactors is dependent on cell type, among others. This review aims to integrate the findings from studies that elucidate ZAP's antiviral role in various viral infections, discuss gaps that need to be filled through further studies, and shed light on new potential targets for therapeutic intervention.
人类中的CCCH型锌指抗病毒蛋白（ZAP），特别是ZAP-L和ZAP-S亚型，是细胞固有免疫反应的关键组成部分。ZAP作为一种转录后RNA限制因子，在逆转录病毒和甲病毒引起的感染过程中发挥其活性。其功能包括与病毒RNA中存在的CpG（胞嘧啶-磷酸-鸟嘌呤）二核苷酸序列结合，从而引导其降解。由于脊椎动物细胞中CpG二核苷酸的频率受到抑制，ZAP能够区分外来遗传元件。ZAP的表达导致病毒复制减少，并阻碍新病毒颗粒的组装。然而，这些作用背后的具体机制尚未完全了解。关于ZAP作用机制的几个问题仍未得到解答，包括CpG二核苷酸数量对ZAP活性的影响、该序列是否是ZAP与病毒RNA结合所唯一必需的，以及辅因子的募集是否依赖于细胞类型等。本综述旨在整合阐明ZAP在各种病毒感染中抗病毒作用的研究结果，讨论需要通过进一步研究填补的空白，并揭示治疗干预的新潜在靶点。
