摘要
单纯疱疹病毒1型(Herpes simplex virus type 1, HSV-1) UL42作为病毒编码的DNA聚合酶辅助亚基之一,是一种多功能蛋白,其在催化和调节病毒在细胞核内的有效复制发挥了重要的作用。已知UL42能提高DNA聚合酶催化亚基UL30的持续合成能力,激活病毒DNA聚合酶活性;介导DNA聚合酶的入核;与DNA模板链结合,提高病毒复制的保真度,以及含有抑制DNA聚合酶活性的肽段,提示其在病毒复制过程中也可能具有负调控作用。近期亦有报道显示,UL42能够阻断肿瘤坏死因子α(tumor necrosis factor-α, TNF-α)激活的核转录因子(nuclear factor kappa-B,NF-κB)信号通路以及干扰素调控因子3(interferon regulatory factor 3, IRF-3)的功能,提示其在病毒逃逸宿主天然免疫反应中发挥了一定的功能,但具体的作用机制尚不明确。本文对目前国内外HSV-1 UL42的结构特点、主要功能、作用机制及其在抗病毒药物研发中的研究进展进行综述,为后续揭示病毒致病机制和抗病毒药物的研发提供参考。
Abstract
Herpes simplex virus type 1 (HSV-1) DNA polymerase accessory subunit UL42 is a multifunctional protein encoded by the viral UL42 gene. It is one of the components of HSV-1 DNA polymerase. HSV-1 UL42 plays an important role in regulating virus replication and in suppressing the host's innate immune response. UL42 is capable of improving the processivity of DNA polymerase catalytic subunit UL30, and functions as a binding mediator between UL30 and DNA template chain, introducing DNA polymerase into nuclear and improving the fidelity of virus replication. In addition, UL42 also contains a peptide which can inhibit the activity of DNA polymerase, suggesting a negative regulatory effect during viral replication. Recent studies indicate that UL42 can block the TNF-α-mediated NF-κB signaling pathway and the function of IRF-3, implying that its ability in evading host’s innate immune response, but the specific mechanism is unclear. A description of research progresses on the structure, functions, mechanism and antiviral drug developments of HSV-1 UL42 could lay a foundation to further researches.
关键词
单纯疱疹病毒1型 /
DNA聚合酶 /
UL42蛋白
张云帆,陈炼凯,张蕊.
单纯疱疹病毒1型DNA聚合酶辅助亚基UL42的研究进展[J]. 微生物与感染. 2021, 16(6): 409-416 https://doi.org/10.3969/j.issn.1673-6184.2021.06.007
ZHANG Yunfan, CHEN Liankai, ZHANG Rui.
Research Progress of Herpes Simplex Virus Type 1 DNA Polymerase Accessory Subunit UL42[J]. Journal of Microbes and Infections. 2021, 16(6): 409-416 https://doi.org/10.3969/j.issn.1673-6184.2021.06.007
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参考文献
基金
国家自然科学基金(项目号31500703);2020年北京市大学生创新训练项目