默克尔细胞多瘤病毒转化和复制的分子机制。
Molecular Mechanisms of Merkel Cell Polyomavirus Transformation and Replication.
机构信息
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6076, USA; email:
出版信息
Annu Rev Virol. 2020 Sep 29;7(1):289-307. doi: 10.1146/annurev-virology-011720-121757. Epub 2020 Jun 30.
Abstract
Viral infection underlies a significant share of the global cancer burden. Merkel cell polyomavirus (MCPyV) is the newest member of the human oncogenic virus family. Its discovery over a decade ago marked the beginning of an exciting era in human tumor virology. Since then, significant evidence has emerged to support the etiologic role of MCPyV in Merkel cell carcinoma (MCC), an extremely lethal form of skin cancer. MCPyV infection is widespread in the general population. MCC diagnoses have tripled over the past 20 years, but effective treatments are currently lacking. In this review, we highlight recent discoveries that have shaped our understanding of MCPyV oncogenic mechanism and host cellular tropism, as well as the molecular events occurring in the viral infectious life cycle. These insights will guide future efforts in developing novel virus-targeted therapeutic strategies for treating the devastating human cancers associated with this new tumorigenic virus.
摘要
病毒感染是全球癌症负担的重要组成部分。 Merkel 细胞多瘤病毒（MCPyV）是人类致癌病毒家族的最新成员。十多年前的发现标志着人类肿瘤病毒学的一个激动人心的时代的开始。从那时起，大量证据支持 MCPyV 在 Merkel 细胞癌（MCC）中的病因作用，MCC 是一种极其致命的皮肤癌。MCPyV 感染在普通人群中广泛存在。在过去的 20 年中，MCC 的诊断增加了两倍，但目前仍缺乏有效的治疗方法。在这篇综述中，我们强调了最近的发现，这些发现塑造了我们对 MCPyV 致癌机制和宿主细胞嗜性以及病毒感染生命周期中发生的分子事件的理解。这些见解将指导未来开发针对这种新致癌病毒相关人类癌症的新型病毒靶向治疗策略的努力。
相似文献
1
Molecular Mechanisms of Merkel Cell Polyomavirus Transformation and Replication.默克尔细胞多瘤病毒转化和复制的分子机制。
Annu Rev Virol. 2020 Sep 29;7(1):289-307. doi: 10.1146/annurev-virology-011720-121757. Epub 2020 Jun 30.
2
Merkel cell polyomavirus: a newly discovered human virus with oncogenic potential.默克尔细胞多瘤病毒：一种具有致癌潜能的新发现的人类病毒。
Virology. 2013 Jan 5;435(1):118-30. doi: 10.1016/j.virol.2012.09.029.
3
Merkel cell polyomavirus and associated Merkel cell carcinoma.默克尔细胞多瘤病毒与相关的默克尔细胞癌。
Tumour Virus Res. 2022 Jun;13:200232. doi: 10.1016/j.tvr.2021.200232. Epub 2021 Dec 15.
4
Merkel cell polyomavirus and non-Merkel cell carcinomas: guilty or circumstantial evidence? Merkel 细胞多瘤病毒与非 Merkel 细胞癌：确凿证据还是间接证据？
APMIS. 2020 Feb;128(2):104-120. doi: 10.1111/apm.13019. Epub 2020 Jan 28.
5
Merkel Cell Polyomavirus and Human Merkel Cell Carcinoma.默克尔细胞多瘤病毒与人类默克尔细胞癌。
Recent Results Cancer Res. 2021;217:303-323. doi: 10.1007/978-3-030-57362-1_12.
6
Infectious Entry of Merkel Cell Polyomavirus. Merkel 细胞多瘤病毒的感染进入。
J Virol. 2019 Mar 5;93(6). doi: 10.1128/JVI.02004-18. Print 2019 Mar 15.
7
The Ubiquitin-Specific Protease Usp7, a Novel Merkel Cell Polyomavirus Large T-Antigen Interaction Partner, Modulates Viral DNA Replication.泛素特异性蛋白酶 Usp7 是一种新型默克尔细胞多瘤病毒大 T 抗原相互作用伙伴，可调节病毒 DNA 复制。
J Virol. 2020 Feb 14;94(5). doi: 10.1128/JVI.01638-19.
8
Merkel Cell Polyomavirus Downregulates N-myc Downstream-Regulated Gene 1, Leading to Cellular Proliferation and Migration. Merkel 细胞多瘤病毒下调 N-myc 下游调节基因 1，导致细胞增殖和迁移。
J Virol. 2020 Jan 17;94(3). doi: 10.1128/JVI.00899-19.
9
Merkel Cell Polyomavirus: A New DNA Virus Associated with Human Cancer.默克尔细胞多瘤病毒：一种与人类癌症相关的新型DNA病毒。
Adv Exp Med Biol. 2017;1018:35-56. doi: 10.1007/978-981-10-5765-6_4.
10
Characterization of the Impact of Merkel Cell Polyomavirus-Induced Interferon Signaling on Viral Infection.描述 Merkel 细胞多瘤病毒诱导的干扰素信号对病毒感染的影响。
J Virol. 2023 Apr 27;97(4):e0190722. doi: 10.1128/jvi.01907-22. Epub 2023 Mar 22.
引用本文的文献
1
IFN γ and the IFN γ Signaling Pathways in Merkel Cell Carcinoma.默克尔细胞癌中的干扰素γ及干扰素γ信号通路
Cancers (Basel). 2025 Aug 1;17(15):2547. doi: 10.3390/cancers17152547.
2
Oncoviruses in the Oral Cavity: Recent Advances in Understanding Viral Infections and Tumorigenesis.口腔中的肿瘤病毒：病毒感染与肿瘤发生认识的最新进展
Int J Mol Sci. 2025 Jul 13;26(14):6721. doi: 10.3390/ijms26146721.
3
Splicing-dependent restriction of the HBZ gene by Tax underlies biphasic HTLV-1 infection.Tax对HBZ基因的剪接依赖性限制是HTLV-1双相感染的基础。
PLoS Pathog. 2025 Jul 28;21(7):e1013381. doi: 10.1371/journal.ppat.1013381. eCollection 2025 Jul.
4
The Role of the Large T Antigen in the Molecular Pathogenesis of Merkel Cell Carcinoma.大 T 抗原在 Merkel 细胞癌分子发病机制中的作用。
Genes (Basel). 2024 Aug 27;15(9):1127. doi: 10.3390/genes15091127.
5
Merkel Cell Polyomavirus in the Context of Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders.口腔鳞状细胞癌和口腔潜在恶性疾病背景下的 Merkel 细胞多瘤病毒
Biomedicines. 2024 Mar 22;12(4):709. doi: 10.3390/biomedicines12040709.
6
The Intricate Interplay between APOBEC3 Proteins and DNA Tumour Viruses.载脂蛋白B编辑酶催化多肽样蛋白3（APOBEC3）家族蛋白与DNA肿瘤病毒之间的复杂相互作用
Pathogens. 2024 Feb 20;13(3):187. doi: 10.3390/pathogens13030187.
7
No detectable truncating mutations in large T antigen (LT-Ag) sequence of Merkel cell polyomavirus (MCPyV) DNA obtained from porocarcinomas.从猪癌中获得的默克尔细胞多瘤病毒（MCPyV）DNA的大T抗原（LT-Ag）序列中未检测到截断突变。
Infect Agent Cancer. 2024 Mar 21;19(1):9. doi: 10.1186/s13027-024-00568-5.
8
Characterization of molecular mechanisms driving Merkel cell polyomavirus oncogene transcription and tumorigenic potential.研究驱动 Merkel 细胞多瘤病毒癌基因转录和致瘤潜能的分子机制。
PLoS Pathog. 2023 Aug 30;19(8):e1011598. doi: 10.1371/journal.ppat.1011598. eCollection 2023 Aug.
9
Detection of Merkel Cell Polyomavirus (MCPyV) DNA and Transcripts in Merkel Cell Carcinoma (MCC).默克尔细胞癌（MCC）中默克尔细胞多瘤病毒（MCPyV）DNA和转录本的检测
Pathogens. 2023 Jun 29;12(7):894. doi: 10.3390/pathogens12070894.
10
Recent Updates on Viral Oncogenesis: Available Preventive and Therapeutic Entities.病毒致癌作用的最新研究进展：现有预防和治疗实体。
Mol Pharm. 2023 Aug 7;20(8):3698-3740. doi: 10.1021/acs.molpharmaceut.2c01080. Epub 2023 Jul 24.
本文引用的文献
1
Conversion of Sox2-dependent Merkel cell carcinoma to a differentiated neuron-like phenotype by T antigen inhibition.通过 T 抗原抑制将 Sox2 依赖性 Merkel 细胞癌转化为分化的神经元样表型。
Proc Natl Acad Sci U S A. 2019 Oct 1;116(40):20104-20114. doi: 10.1073/pnas.1907154116. Epub 2019 Sep 16.
2
MCPyV Large T Antigen-Induced Atonal Homolog 1 Is a Lineage-Dependency Oncogene in Merkel Cell Carcinoma.MCPyV 大 T 抗原诱导的 Atonal Homolog 1 是 Merkel 细胞癌中的谱系依赖性癌基因。
J Invest Dermatol. 2020 Jan;140(1):56-65.e3. doi: 10.1016/j.jid.2019.06.135. Epub 2019 Jul 5.
3
Merkel Cell Polyomavirus Infection and Detection.默克尔细胞多瘤病毒感染与检测
J Vis Exp. 2019 Feb 7(144). doi: 10.3791/58950.
4
Merkel cell polyomavirus Tumor antigens expressed in Merkel cell carcinoma function independently of the ubiquitin ligases Fbw7 and β-TrCP.Merkel 细胞多瘤病毒——在 Merkel 细胞癌中表达的肿瘤抗原——独立于泛素连接酶 Fbw7 和 β-TrCP 发挥作用。
PLoS Pathog. 2019 Jan 28;15(1):e1007543. doi: 10.1371/journal.ppat.1007543. eCollection 2019 Jan.
5
Infectious Entry of Merkel Cell Polyomavirus. Merkel 细胞多瘤病毒的感染进入。
J Virol. 2019 Mar 5;93(6). doi: 10.1128/JVI.02004-18. Print 2019 Mar 15.
6
Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 response.病毒阳性 Merkel 细胞癌中 MDM2 和 MDM4 的双重抑制增强了 p53 反应。
Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):1027-1032. doi: 10.1073/pnas.1818798116. Epub 2018 Dec 31.
7
Novel Human Polyomavirus Noncoding Control Regions Differ in Bidirectional Gene Expression according to Host Cell, Large T-Antigen Expression, and Clinically Occurring Rearrangements.新型人类多瘤病毒非编码控制区在双向基因表达上因宿主细胞、大T抗原表达及临床出现的重排而异。
J Virol. 2018 Mar 14;92(7). doi: 10.1128/JVI.02231-17. Print 2018 Apr 1.
8
Merkel Cell Polyomavirus Infection of Animal Dermal Fibroblasts.默克尔细胞多瘤病毒感染动物真皮成纤维细胞。
J Virol. 2018 Jan 30;92(4). doi: 10.1128/JVI.01610-17. Print 2018 Feb 15.
9
Merkel cell carcinoma: Current US incidence and projected increases based on changing demographics.默克尔细胞癌：基于人口结构变化的美国当前发病率和预计增长。
J Am Acad Dermatol. 2018 Mar;78(3):457-463.e2. doi: 10.1016/j.jaad.2017.10.028. Epub 2017 Nov 2.
10
Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesis.默克尔细胞多瘤病毒将MYCL招募至EP400复合物以促进肿瘤发生。
PLoS Pathog. 2017 Oct 13;13(10):e1006668. doi: 10.1371/journal.ppat.1006668. eCollection 2017 Oct.
Zotero 插件