An Overview of the Unfolded Protein Response (UPR) and Autophagy Pathways in Human Viral Oncogenesis.

3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Shovan Dutta, Anirban Ganguly, Sounak Ghosh Roy
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引用次数: 0

Abstract

Autophagy and Unfolded Protein Response (UPR) can be regarded as the safe keepers of cells exposed to intense stress. Autophagy maintains cellular homeostasis, ensuring the removal of foreign particles and misfolded macromolecules from the cytoplasm and facilitating the return of the building blocks into the system. On the other hand, UPR serves as a shock response to prolonged stress, especially Endoplasmic Reticulum Stress (ERS), which also includes the accumulation of misfolded proteins in the ER. Since one of the many effects of viral infection on the host cell machinery is the hijacking of the host translational system, which leaves in its wake a plethora of misfolded proteins in the ER, it is perhaps not surprising that UPR and autophagy are common occurrences in infected cells, tissues, and patient samples. In this book chapter, we try to emphasize how UPR, and autophagy are significant in infections caused by six major oncolytic viruses-Epstein-Barr (EBV), Human Papilloma Virus (HPV), Human Immunodeficiency Virus (HIV), Human Herpesvirus-8 (HHV-8), Human T-cell Lymphotropic Virus (HTLV-1), and Hepatitis B Virus (HBV). Here, we document how whole-virus infection or overexpression of individual viral proteins in vitro and in vivo models can regulate the different branches of UPR and the various stages of macro autophagy. As is true with other viral infections, the relationship is complicated because the same virus (or the viral protein) exerts different effects on UPR and Autophagy. The nature of this response is determined by the cell types, or in some cases, the presence of diverse extracellular stimuli. The vice versa is equally valid, i.e., UPR and autophagy exhibit both anti-tumor and pro-tumor properties based on the cell type and other factors like concentrations of different metabolites. Thus, we have tried to coherently summarize the existing knowledge, the crux of which can hopefully be harnessed to design vaccines and therapies targeted at viral carcinogenesis.

人类病毒肿瘤发生过程中的折叠蛋白反应(UPR)和自噬途径概述。
自噬和未折叠蛋白反应(UPR)可被视为暴露在强烈压力下的细胞的安全守护者。自噬能维持细胞的平衡,确保将外来颗粒和折叠错误的大分子从细胞质中清除,并促进构件回到系统中。另一方面,UPR 是对长期应激,特别是内质网应激(ERS)的一种休克反应,其中也包括错误折叠蛋白质在内质网中的积累。由于病毒感染对宿主细胞机制的诸多影响之一是劫持宿主的翻译系统,从而在内质网中留下大量错误折叠的蛋白质,因此,UPR 和自噬在感染细胞、组织和患者样本中的常见现象也许就不足为奇了。在本书的这一章中,我们试图强调 UPR 和自噬在六种主要溶瘤病毒--爱泼斯坦-巴氏病毒(EBV)、人类乳头状瘤病毒(HPV)、人类免疫缺陷病毒(HIV)、人类疱疹病毒-8(HHV-8)、人类 T 细胞淋巴细胞病毒(HTLV-1)和乙型肝炎病毒(HBV)--引起的感染中的重要作用。在这里,我们记录了在体外和体内模型中,全病毒感染或过表达单个病毒蛋白如何调节 UPR 的不同分支以及宏自噬的不同阶段。与其他病毒感染一样,这种关系也很复杂,因为同一种病毒(或病毒蛋白)会对 UPR 和自噬产生不同的影响。这种反应的性质由细胞类型决定,或者在某些情况下由不同的细胞外刺激决定。反之亦然,即 UPR 和自噬根据细胞类型和其他因素(如不同代谢物的浓度)表现出抗肿瘤和促肿瘤的特性。因此,我们试图对现有知识进行连贯的总结,希望可以利用其中的关键点来设计针对病毒致癌的疫苗和疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International review of cell and molecular biology
International review of cell and molecular biology BIOCHEMISTRY & MOLECULAR BIOLOGY-CELL BIOLOGY
CiteScore
7.70
自引率
0.00%
发文量
67
审稿时长
>12 weeks
期刊介绍: International Review of Cell and Molecular Biology presents current advances and comprehensive reviews in cell biology-both plant and animal. Articles address structure and control of gene expression, nucleocytoplasmic interactions, control of cell development and differentiation, and cell transformation and growth. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research.
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