Research Progress on Endoplasmic Reticulum Stress/Unfolded Protein Response Caused by Herpesvirus

doi:10.13304/j.nykjdb.2022.0538

Abstract

Abstract:

Endoplasmic reticulum is the main site of protein folding and post-translational modification in eukaryotic cells. It also participates in the regulation of Ca²⁺ and lipid storage and synthesis， and has important physiological functions. Herpesviruses is a class of enveloped DNA viruses. The synthesis and processing of its surface glycosylated envelope proteins depends on the endoplasmic reticulum. During virus replication， a large number of synthesized glycosylated envelope proteins are excessive in the endoplasmic reticulum. Accumulation causes endoplasmic reticulum stress （ERS）， which in turn leads to unfolded protein response （UPR）. Some herpesviruses may have evolved mechanisms to regulate the UPR to create an optimal egoistic environment for the replication process. When they replicate in host cells， they will cause related endoplasmic reticulum UPR signaling cascades， such as cell damage， inflammation， apoptosis， etc. In this paper， the mechanism of endoplasmic reticulum stress/unfolded protein response （ERS/UPR） response to viruses was reviewed， and the molecular mechanism and related signaling pathways of ERS caused by herpes simplex virus type Ⅰ， pseudorabies virus， marek virus， duck enteritis virus and other herpes viruses were expounded， which provided theoretical basis for the research and development of herpes virus-related vaccines and drug targets.

Key words: endoplasmic reticulum stress, unfolded protein response, herpesvirus

摘要：

内质网是真核细胞内蛋白质折叠及翻译后修饰的主要场所，还参与调控Ca²⁺和脂类物质储存合成，具有重要生理功能。疱疹病毒是一类具有囊膜的DNA病毒，其表面糖基化囊膜蛋白的合成加工依赖于内质网，在病毒复制过程中，大量合成的糖基化囊膜蛋白在内质网内过度堆积则会引起内质网应激（endoplasmic reticulum stress，ERS），进而发生未折叠蛋白反应（unfolded protein response，UPR）。某些疱疹病毒可能已经进化出调控UPR的机制，为复制过程创造最佳环境，它们在宿主细胞内复制时，会引起相关内质网UPR信号级联反应，如细胞损伤、炎症反应、细胞凋亡等。综述了内质网应激/未折叠蛋白（ERS/UPR）对病毒的反应机制，从Ⅰ型单纯疱疹病毒、伪狂犬病病毒、马立克病病毒、鸭肠炎病毒和其他疱疹病毒等感染引起ERS分子机制及相关信号通路进行阐述，以期为疱疹病毒相关疫苗和药物作用靶点的研发提供理论依据。

关键词: 内质网应激, 未折叠蛋白反应, 疱疹病毒

CLC Number:

S432.4⁺1

Haiqing CAI, Wei WANG, Maoqin ZENG, Wenwen BI, Li CHEN, Qiandong ZHANG, Yang YUAN, Ming WEN. Research Progress on Endoplasmic Reticulum Stress/Unfolded Protein Response Caused by Herpesvirus[J]. Journal of Agricultural Science and Technology, 2023, 25(9): 131-139.

蔡海情, 王微, 曾茂芹, 毕文文, 陈莉, 张黔东, 袁阳, 文明. 疱疹病毒引起内质网应激/未折叠蛋白反应研究进展[J]. 中国农业科技导报, 2023, 25(9): 131-139.

Figures/Tables 2

References 63

1	GATHERER D, DEPLEDGE D P, HARTLEY C A, et al.. ICTV virus taxonomy profile: Herpesviridae 2021 [J/OL]. J. Gen. Virol. , 2021, 102(10):1673 [2022-05-28]. .
2	CONNOLLY S A, JARDETZKY T S, LONGNECKER R. The structural basis of Herpesvirus entry [J]. Nat. Rev. Microbiol., 2021, 19(2): 110-121.
3	KRUG L T, PELLETT P E. The family Herpesviridae: a brief introduction [J]. Fields Virol., 2021, 2: 212-234.
4	JOHNSTON B P, MCCORMICK C. Herpesviruses and the unfolded protein response [J/OL]. Viruses, 2019, 12(1):17 [2022-05-28]. .
5	牛宇辉, 李向茸, 冯若飞. 人类疱疹病毒逃逸宿主抗病毒固有免疫应答机制的研究进展[J]. 中国人兽共患病学报, 2022,38(1):62-68.
	NIU Y H, LI X R, FENG R F. Research progress in the mechanism through which human herpesvirus escape the host antiviral innate immune response [J]. Chin. J. Zoonoses, 2022,38(1):62-68.
6	王文婧, 范青松, 刘宇航, 等. 去泛素化酶UL36的抑制剂LDN57444抑制马立克氏病病毒的增殖[J]. 中国兽医学报, 2022, 42(10): 1949-1957.
	WANG W J, FAN Q S, LIU Y H, et al.. Suppression of replication of Marek’s disease virus by deubiquitinase UL36 inhibitor LDN57444 [J]. Chin. J. Vet. Sci., 2022, 42(10): 1949-1957.
7	WANG D, HUO H, WERID G M, et al.. TBK1 mediates innate antiviral immune response against duck enteritis virus: viruses [J/OL]. 2022: 14(5): 1008 [2022-05-28]. .
8	谷思睿, 赵军, 陈弟诗, 等. 伪狂犬病毒潜伏感染相关病毒因子研究进展[J]. 病毒学报, 2021,37(6):1515-1524.
	GU S R, ZHAO J, CHEN D S, et al.. Research progress on viral factors associated with Pseudorabies virus latent infection [J]. Chin. J. Virol., 2021, 37(6): 1515-1524.
9	SONG S, TAN J, MIAO Y, et al.. Crosstalk of ER stress-mediated autophagy and ER-phagy: involvement of UPR and the core autophagy machinery [J]. J. Cell Physiol., 2018, 233(5): 3867-3874.
10	D'ORAZI G, CIRONE M. Interconnected adaptive responses: a way out for cancer cells to avoid cellular demise [J/OL]. Cancers (Basel), 2022, 14(11): 14112780 [2022-05-28]. .
11	HETZ C, ZHANG K, KAUFMAN R J. Mechanisms, regulation and functions of the unfolded protein response [J]. Nat. Rev. Mol. Cell Biol., 2020, 21(8): 421-438.
12	HARDING H P, CALFON M, URANO F, et al.. Transcriptional and translational control in the mammalian unfolded protein response [J]. Annu. Rev. Cell Dev. Biol., 2002, 18: 575-599.
13	CIRONE M. Cancer cells dysregulate PI3K/AKT/mTOR pathway activation to ensure their survival and proliferation: mimicking them is a smart strategy of gammaherpesviruses [J]. Crit. Rev. Biochem. Mol. Biol., 2021, 56(5): 500-509.
14	CIRONE M. ER stress, UPR activation and the inflammatory response to viral infection [J/OL]. Viruses, 2021, 13(5):798 [2022-05-28]. .
15	SU A, WANG H, ZHENG D, et al.. TUDCA inhibits HSV-1 replication by the modulating unfolded protein response pathway [J/OL]. J. Med. Virol., 2020,5: 25963 [2022-05-28]. .
16	CHEN S, LI X, ZHANG X, et al.. PCV2 and PRV coinfection induces endoplasmic reticulum stress via PERK-eIF2α-ATF4-CHOP and IRE1-XBP1-EDEM pathways [J/OL]. Int. J. Mol. Sci., 2022, 23(9): 94479 [2022-05-28]. .
17	NEERUKONDA S N, KATNENI U K, BOTT M, et al.. Induction of the unfolded protein response (UPR) during Marek's disease virus (MDV) infection [J]. Virology, 2018, 522: 1-12.
18	ZHANG Y, WANG X, HU A, et al.. Duck enteritis virus infection suppresses viability and induces apoptosis and endoplasmic reticulum stress in duck embryo fibroblast cells via the regulation of Ca²⁺ [J]. J. Vet. Med. Sci, 2021,83(3):549-557.
19	QI Z, CHEN L. Endoplasmic reticulum stress and autophagy [J]. Adv. Exp. Med. Biol., 2019, 1206:167-177.
20	LI S, KONG L, YU X. The expanding roles of endoplasmic reticulum stress in virus replication and pathogenesis [J]. Crit. Rev. Microbiol., 2015, 41(2): 150-164.
21	AYDIN Y, KURT R, SONG K, et al.. Hepatic stress response in HCV infection promotes STAT3-mediated inhibition of HNF4A-miR-122 feedback loop in liver fibrosis and cancer progression [J/OL]. Cancers (Basel), 2019, 11(10):1407 [2022-05-28]. .
22	ZHENG Y, LI S, LI S H, et al.. Transcriptome profiling in swine macrophages infected with African swine fever virus at single-cell resolution [J/OL]. Proc. Natl. Acad. Sci. USA, 2022, 119(19): e2093679177 [2022-05-28]. .
23	BAUDI I, ISOGAWA M, MOALLI F, et al.. Interferon signaling suppresses the unfolded protein response and induces cell death in hepatocytes accumulating hepatitis B surface antigen [J/OL]. PLoS Pathog., 2021, 17(5):1009228 [2022-05-28]. .
24	BLÁZQUEZ A B, ESCRIBANO-ROMERO E, MERINO-RAMOS T, et al.. Stress responses in flavivirus-infected cells: activation of unfolded protein response and autophagy [J/OL]. Front. Microbiol., 2014,5:266 [2022-05-28]. .
25	NAUGHTON M, MCMAHON J, HEALY S, et al.. Profile of the unfolded protein response in rat cerebellar cortical development [J]. J. Comp. Neurol., 2019, 527(17): 2910-2924.
26	BERTOLOTTI A, ZHANG Y, HENDERSHOT L M, et al.. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response [J]. Nat. Cell Biol., 2000, 2(6): 326-332.
27	WALTER P, RON D. The unfolded protein response: from stress pathway to homeostatic regulation [J]. Science, 2011, 334(6059): 1081-1086.
28	GARDNER B M, WALTER P. Unfolded proteins are Ire1-activating ligands that directly induce the unfolded protein response [J]. Science, 2011, 333(6051): 1891-1894.
29	READ A, SCHRÖDER M. The unfolded protein response: an overview [J/OL]. Biology (Basel), 2021, 10(5): 10050384 [2022-05-28]. .
30	BERNALES S, PAPA F R, WALTER P. Intracellular signaling by the unfolded protein response [J]. Annu. Rev. Cell Dev. Biol., 2006, 22: 487-508.
31	LIN J H, WALTER P, YEN T S. Endoplasmic reticulum stress in disease pathogenesis [J]. Annu. Rev. Pathol., 2008, 3: 399-425.
32	TIAN F, ZHAO J, BU S, et al.. KLF6 induces apoptosis in human lens epithelial cells through the ATF4-ATF3-CHOP axis [J]. Drug. Des. Devel. Ther., 2020, 14: 1041-1055.
33	ROZPEDEK W, PYTEL D, MUCHA B, et al.. The role of the PERK/eIF2α/ATF4/CHOP signaling pathway in tumor progression during endoplasmic reticulum stress [J]. Curr. Mol. Med., 2016, 16(6): 533-544.
34	HU H, TIAN M, DING C, et al.. The C/EBP homologous protein (CHOP) transcription factor functions in endoplasmic reticulum stress-induced apoptosis and microbial infection [J/OL]. Front. Immunol., 2018, 9: 3083 [2022-05-28]. .
35	UBEDA M, WANG X Z, ZINSZNER H, et al.. Stress-induced binding of the transcriptional factor CHOP to a novel DNA control element [J]. Mol. Cell Biol., 1996, 16(4): 1479-1489.
36	MATSUMOTO M, MINAMI M, TAKEDA K, et al.. Ectopic expression of CHOP (GADD153) induces apoptosis in M1 myeloblastic leukemia cells [J]. FEBS Lett., 1996, 395(2-3): 143-147.
37	LI G, MONGILLO M, CHIN K T, et al.. Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis [J]. J. Cell Biol., 2009, 186(6): 783-792.
38	OYADOMARI S, MORI M. Roles of CHOP/GADD153 in endoplasmic reticulum stress [J]. Cell Death Differ., 2004, 11(4): 381-389.
39	CHEN Y, BRANDIZZI F. IRE1: ER stress sensor and cell fate executor [J]. Trends Cell Biol., 2013, 23(11): 547-555.
40	ALMANZA A, CARLESSO A, CHINTHA C, et al.. Endoplasmic reticulum stress signalling-from basic mechanisms to clinical applications [J]. FEBS J., 2019, 286(2): 241-278.
41	KOPP M C, LARBURU N, DURAIRAJ V, et al.. UPR proteins IRE1 and PERK switch BiP from chaperone to ER stress sensor [J]. Nat. Struct. Mol. Biol., 2019, 26(11): 1053-1062.
42	BASHIR S, BANDAY M, QADRI O, et al.. The molecular mechanism and functional diversity of UPR signaling sensor IRE1 [J/OL]. Life Sci., 2021, 265: 118740 [2022-05-28]. .
43	TANG C H, CHANG S, PATON A W, et al.. Phosphorylation of IRE1 at S729 regulates RIDD in B cells and antibody production after immunization [J]. J. Cell Biol., 2018, 217(5): 1739-1755.
44	KORENNYKH A V, KOROSTELEV A A, EGEA P F, et al.. Structural and functional basis for RNA cleavage by Ire1 [J/OL]. BMC Biol., 2011, 9:47 [2022-05-28]..
45	PATTINGRE S, TASSA A, QU X, et al.. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy [J]. Cell, 2005, 122(6): 927-939.
46	SAEED M, SUZUKI R, WATANABE N, et al.. Role of the endoplasmic reticulum-associated degradation (ERAD) pathway in degradation of hepatitis C virus envelope proteins and production of virus particles [J]. J. Biol. Chem., 2011, 286(43): 37264-37273.
47	TAN Z, ZHANG W, SUN J, et al.. ZIKV infection activates the IRE1-XBP1 and ATF6 pathways of unfolded protein response in neural cells [J/OL]. J. Neuroinflammation, 2018, 15(1): 275 [2022-05-28]. .
48	SO J S. Roles of endoplasmic reticulum stress in immune responses [J]. Mol. Cells, 2018, 41(8): 705-716.
49	CONZA G D, HO P C. ER stress responses: an Emerging modulator for innate immunity [J/OL]. Cells, 2020,9(3): 9030695 [2022-05-28]. .
50	FRABUTT D A, ZHENG Y H. Arms race between enveloped viruses and the host ERAD machinery [J/OL]. Viruses, 2016, 8(9): 8090255 [2022-05-28]. .
51	BURNETT H F, AUDAS T E, LIANG G, et al.. Herpes simplex virus-1 disarms the unfolded protein response in the early stages of infection [J]. Cell Stress Chaperon., 2012, 17(4): 473-483.
52	ZHANG P, SU C, JIANG Z, et al.. Herpes simplex virus 1 UL41 protein suppresses the IRE1/XBP1 signal pathway of the unfolded protein response via its RNase activity [J/OL]. J. Virol., 2017, 91(4):16 [2022-05-28]. .
53	HU F, YU X, WANG H, et al.. ER stress and its regulator X-box-binding protein-1 enhance polyIC-induced innate immune response in dendritic cells [J]. Eur. J. Immunol., 2011, 41(4): 1086-1097.
54	YANG S, ZHU J, ZHOU X, et al.. Induction of the unfolded protein response (UPR) during pseudorabies virus infection [J/OL]. Vet. Microbiol., 2019, 239: 108485 [2022-05-28]. .
55	ABDUL-CAREEM M F, HUNTER B D, SARSON A J, et al.. Marek’s disease virus-induced transient paralysis is associated with cytokine gene expression in the nervous system [J]. Viral Immunol., 2006, 19(2): 167-176.
56	DHAMA K, KUMAR N, SAMINATHAN M, et al.. Duck virus enteritis (duck plague)—a comprehensive update [J]. Vet. Quarterly, 2017,37(1):57-80.
57	YIN H, ZHAO L, JIANG X, et al.. DEV induce autophagy via the endoplasmic reticulum stress related unfolded protein response [J/OL]. PLoS One, 2017, 12(12): e189704 [2022-05-28]. .
58	ROMEO M A, SANTARELLI R, GILARDINI M M, et al.. Viral infection and autophagy dysregulation: the case of HHV-6, EBV and KSHV [J/OL]. Cells, 2020, 9(12): 9122624 [2022-05-28]. .
59	SANTARELLI R, ARTENI A, GILARDINI M M, et al.. KSHV dysregulates bulk macroautophagy, mitophagy and UPR to promote endothelial to mesenchymal transition and CCL2 release, key events in viral-driven sarcomagenesis [J]. Int. J. Cancer, 2020, 147(12): 3500-3510.
60	SIDDIQUEY M N A, ZHANG H, NGUYEN C C, et al.. The human cytomegalovirus endoplasmic reticulum-resident glycoprotein UL148 activates the unfolded protein response [J/OL]. J. Virol., 2018,92(20): e00896-18 [2022-05-28]. .
61	ZHANG H, READ C, NGUYEN C C, et al.. The human cytomegalovirus nonstructural glycoprotein UL148 reorganizes the endoplasmic reticulum [J/OL]. mBio, 2019, 10(6):e02110-19 [2022-05-28]. .
62	CARPENTER J E, GROSE C. Varicella-zoster virus glycoprotein expression differentially induces the unfolded protein response in infected cells [J/OL]. Front. Microbiol., 2014,5:322 [2022-05-28]. .
63	HOJI A, XU S, BILBEN H, et al.. Calcium mobilization is responsible for thapsigargin induced Epstein Barr virus lytic reactivation in in vitro immortalized lymphoblstoid cell lines [J/OL]. Heliyon, 2018, 4(11):e00917 [2022-05-28]. .