Research progress on the mechanism of cytomegalovirus immuneevasion

doi:10.3877/cma.j.issn.1674-1358.2023.02.001

Abstract

Abstract:

Cytomegalovirus (CMV) is a widespread pathogen that persists as a lifelong latent infection. In immunocompromised individuals, CMV can reactivate and cause substantial immunological changes in the host, resulting in serious clinical complications and death. During the long evolution process of the virus and the host, the virus has developed complex mechanisms to evade the host immune system. Owing to the huge genome, CMV expresses various components that resist the host immuneresponse effectively. Morever, CMV also exploits host cells to resist the immmune response. The main mechanisms include: down-regulating the expressions of major histocompatibility complex, T cell exhaustion, escaping from the host interferon response, inhibiting the functions of natural killer cells and dendritic cells, impairing humoral immunity, etc. Studying on the mechanism of CMV immune evasion is of great significance to the prevention and treatment of CMV infection. This article reviews research progress on the mechanism of CMV immune evasion, and probes into the occurrence, development and outcomes of the interaction between the virus and the host.

Key words: Cytomegalovirus infection, Immune evasion

Yan Chen, Xiaochun Shi, Xiaoqing Liu. Research progress on the mechanism of cytomegalovirus immuneevasion[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2023, 17(02): 73-78.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhsyhlcgrbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-1358.2023.02.001

https://zhsyhlcgrbzz.cma-cmc.com.cn/EN/Y2023/V17/I02/73

References 56

[1]	Sinzger C, Digel M, Jahn G. Cytomegalovirus cell tropism[J]. Curr Top Microbiol Immunol,2008,325:63-83.
[2]	Stern L, Withers B, Avdic S, et al. Human cytomegalovirus latency and reactivation in allogeneic hematopoietic stem cell transplant recipients[J]. Front Microbiol,2019,10:1186.
[3]	Fang FQ, Fan QS, Yang ZJ, et al. Incidence of cytomegalovirus infection in Shanghai, China[J]. Clin Vaccine Immunol,2009,16(11):1700-1703.
[4]	Han SH, Yoo SG, Do Han K, et al. The incidence and effect of cytomegalovirus disease on mortality in transplant recipients and general population: real-world nationwide cohort data[J]. Int J Med Sci,2021,18(14):3333-3341.
[5]	Da Cunha T, Wu GY. Cytomegalovirus hepatitis in immunocompetent and immunocompromised hosts[J]. J Clin Transl Hepatol,2021,9(1):106-115.
[6]	谭雨亭, 侍效春, 刘晓清, 等. 系统性红斑狼疮合并巨细胞病毒感染的临床特征及危险因素[J]. 中国医学科学院学报,2020,42(6):749-754.
[7]	Gabor F, Jahn G, Sedmak DD, et al. In vivo downregulation of MHC class Ⅰmolecules by HCMV occurs during all phases of viral replication but is not always complete[J]. Front Cell Infect Microbiol,2020,10:283.
[8]	Ameres S, Besold K, Plachter B, et al. CD8 T cell-evasive functions of human cytomegalovirus display pervasive MHC allele specificity, complementarity, and cooperativity[J]. J Immunol,2014,192(12):5894-5905.
[9]	Hsu JL, Van Den Boomen DJ, Tomasec P, et al. Plasma membrane profiling defines an expanded class of cell surface proteins selectively targeted for degradation by HCMV US2 in cooperation with UL141[J]. PLoS Pathog,2015,11(4):e1004811.
[10]	Kalejta RF, Albright ER. Expanding the known functional repertoire of the human cytomegalovirus pp71 protein[J]. Front Cell Infect Microbiol,2020,10:95.
[11]	Melaiu O, D'Amico S, Tempora P, et al. Impact of natural occurring ERAP1 single nucleotide polymorphisms within miRNA-binding sites on HCMV infection[J]. Int J Mol Sci,2020,21(16):5861.
[12]	Poole E, Neves TC, Oliveira MT, et al. Human cytomegalovirus interleukin 10 homologs: facing the immune system[J]. Front Cell Infect Microbiol,2020,10:245.
[13]	Yunis J, Farrell HE, Bruce K, et al. Murine cytomegalovirus degrades MHC class Ⅱ to colonize the salivary glands[J]. PLoS Pathog,2018,14(2):e1006905.
[14]	Lim EY, Jackson SE, Wills MR. The CD4⁺ T cell response to human cytomegalovirus in healthy and immunocompromised people[J]. Front Cell Infect Microbiol,2020,10:202.
[15]	Sandhu PK, Buchkovich NJ. Human cytomegalovirus decreases major histocompatibility complex class Ⅱ by regulating class Ⅱ transactivator transcript levels in a myeloid cell line[J]. J Virol,2020,94(7):e01901-19.
[16]	Sarango G, Richetta C, Pereira M, et al. The autophagy receptor TAX1BP1 (T6BP) improves antigen presentation by MHC-Ⅱ molecules[J]. EMBO Rep,2022,23(12):e55470.
[17]	洪淑君, 陈名武. IL-10在巨细胞病毒感染中的免疫机制研究进展[J]. 国际儿科学杂志,2016,43(6):434-436.
[18]	Wehrens EJ, Wong KA, Gupta A, et al. IL-27 regulates the number, function and cytotoxic program of antiviral CD4 T cells and promotes cytomegalovirus persistence[J]. PLoS One,2018,13(7):e0201249.
[19]	Rollings CM, Sinclair LV, Brady HJM, et al. Interleukin-2 shapes the cytotoxic T cell proteome and immune environment-sensing programs[J]. Sci Signal,2018,11(526):eaap8112.
[20]	Kalia V, Sarkar S. Regulation of effector and memory CD8 T cell differentiation by IL-2-A balancing act[J]. Front Immunol,2018,9:2987.
[21]	Hashimoto M, Araki K, Cardenas MA, et al. PD-1 combination therapy with IL-2 modifies CD8(+) T cell exhaustion program[J]. Nature,2022,610(7930):173-181.
[22]	West EE, Jin HT, Rasheed AU, et al. PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells[J]. J Clin Invest,2013,123(6):2604-2615.
[23]	Hernandez R, Põder J, Laporte KM, et al. Engineering IL-2 for immunotherapy of autoimmunity and cancer[J]. Nat Rev Immunol,2022,22(10):614-628.
[24]	Choi YJ, Kim SB, Kim JH, et al. Impaired polyfunctionality of CD8(+) T cells in severe sepsis patients with human cytomegalovirus reactivation[J]. Exp Mol Med,2017,49(9):e382.
[25]	Murata T. Human herpesvirus and the immune checkpoint PD-1/PD-L1 pathway: disorders and strategies for survival[J]. Microorganisms,2021,9(4):778.
[26]	Jin HT, Anderson AC, Tan WG, et al. Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection[J]. Proc Natl Acad Sci USA,2010,107(33):14733-14738.
[27]	Avery L, Filderman J, Szymczak Workman AL, et al. Tim-3 co-stimulation promotes short-lived effector T cells, restricts memory precursors, and is dispensable for T cell exhaustion[J]. Proc Natl Acad Sci USA,2018,115(10):2455-2460.
[28]	Kataoka S, Manandhar P, Lee J, et al. The costimulatory activity of Tim-3 requires Akt and MAPK signaling and its recruitment to the immune synapse[J]. Sci Signal,2021,14(687):eaba0717.
[29]	Lerner AH, Farmakiotis D. CMV cell-mediated immunity assays: Focus on CD4(+) cells[J]. Am J Transplant,2020,20(8):2285-2286.
[30]	王凛介, 朱科达, 刘风云, 等. 系统性红斑狼疮患者不同巨细胞病毒感染状态淋巴细胞亚群分析[J/CD]. 中华实验和临床感染病杂志(电子版),2020,14(6):501-506.
[31]	Tovar Salazar A, Weinberg A. Understanding the mechanism of action of cytomegalovirus-induced regulatory T cells[J]. Virology,2020,547:1-6.
[32]	朱莉莉, 徐玲, 王军. HCMV感染患儿HLA-DR,CD4+CD25+调节性T细胞及IL-17, IL-27表达水平与肝损害的相关性研究[J]. 中国当代儿科杂志,2018,20(7):554-558.
[33]	于仲勋, 宋红梅. 认识Ⅰ型干扰素病[J]. 中华实用儿科临床杂志,2022,37(1):2-5.
[34]	Jiang G, Gong M, Song H, et al. Tob2 inhibits TLR-induced inflammatory responses by association with TRAF6 and MyD88[J]. J Immunol,2020,205(4):981-986.
[35]	Zhang X, Bai XC, Chen ZJ. Structures and mechanisms in the cGAS-STING innate immunity pathway[J]. Immunity,2020,53(1):43-53.
[36]	Gao D, Ciancanelli MJ, Zhang P, et al. TLR3 controls constitutive IFN-β antiviral immunity in human fibroblasts and cortical neurons[J]. J Clin Invest,2021,131(1):e134529.
[37]	Castón JJ, Cantisán S, González-gasca F, et al. Interferon-γ production by CMV-specific CD8⁺ T lymphocytes provides protection against cytomegalovirus reactivation in critically ill patients[J]. Intensive Care Med,2016,42(1):46-53.
[38]	Chemaly RF, El Haddad L, Winston DJ, et al. Cytomegalovirus (CMV) cell-mediated immunity and CMV infection after allogeneic hematopoietic cell transplantation: the REACT study[J]. Clin Infect Dis,2020,71(9):2365-2374.
[39]	Liu Y, Ye S, Zhou B, et al. The establishment of CMV antigen-specific enzyme-linked immunospot assay among Chinese: A pilot study[J]. Clin Chim Acta,2020,500:143-148.
[40]	卢元元, 舒赛男. 人巨细胞病毒在逃避宿主干扰素信号方面的研究进展[J]. 中华实用儿科临床杂志,2022,37(11):878-880.
[41]	Zou HM, Huang ZF, Yang Y, et al. Human cytomegalovirus protein UL94 targets MITA to evade the antiviral immune response[J]. J Virol,2020,94(12):e00022-20.
[42]	Ren Y, Wang A, Wu D, et al. Dual inhibition of innate immunity and apoptosis by human cytomegalovirus protein UL37x1 enables efficient virus replication[J]. Nat Microbiol,2022,7(7):1041-1053.
[43]	Patel M, Vlahava VM, Forbes SK, et al. HCMV-encoded NK modulators: lessons from in vitro and in vivo genetic variation[J]. Front Immunol,2018,9:2214.
[44]	Umashankar M, Rak M, Bughio F, et al. Antagonistic determinants controlling replicative and latent states of human cytomegalovirus infection[J]. J Virol,2014,88(11):5987-6002.
[45]	Dassa L, Seidel E, Oiknine Djian E, et al. The human cytomegalovirus protein UL148A downregulates the NK cell-activating ligand MICA to avoid NK cell attack[J]. J Virol,2018,92(17):e00162-18.
[46]	Wang ECY, Pjechova M, Nightingale K, et al. Suppression of costimulation by human cytomegalovirus promotes evasion of cellular immune defenses[J]. Proc Natl Acad Sci USA,2018,115(19): 4998-5003.
[47]	Becker S, Fink A, Podlech J, et al. Host-adapted gene families involved in murine cytomegalovirus immune evasion[J]. Viruses, 2022,14(1):128.
[48]	Berry R, Vivian JP, Deuss FA, et al. The structure of the cytomegalovirus-encoded m04 glycoprotein, a prototypical member of the m02 family of immunoevasins[J]. J Biol Chem,2014, 289(34):23753-23763.
[49]	Hammer Q, Rückert T, Borst EM, et al. Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells[J]. Nat Immunol,2018,19(5):453-463.
[50]	Andrews DM, Andoniou CE, Granucci F, et al. Infection of dendritic cells by murine cytomegalovirus induces functional paralysis[J]. Nat Immunol,2001,2(11):1077-1084.
[51]	Mathys S, Schroeder T, Ellwart J, et al. Dendritic cells under influence of mouse cytomegalovirus have a physiologic dual role: to initiate and to restrict T cell activation[J]. J Infect Dis,2003,187(6):988-999.
[52]	Avdic S, Mcsharry BP, Slobedman B. Modulation of dendritic cell functions by viral IL-10 encoded by human cytomegalovirus[J]. Front Microbiol,2014,5:337.
[53]	Vajger U, Roman PJ. Recent discoveries in dendritic cell tolerance-inducing pharmacological molecules[J]. Int Immunopharmacol, 2020,81:106275.
[54]	Corrales Aguilar E, Trilling M, Hunold K, et al. Human cytomegalovirus Fcγ binding proteins gp34 and gp68 antagonize Fcγ receptors Ⅰ, Ⅱ and Ⅲ[J]. PLoS Pathog,2014,10(5):e1004131.
[55]	Liu X, Palaniyandi S, Zhu I, et al. Human cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptor[J]. Nat Commun,2019,10(1):3020.
[56]	Raanani P, Gafter-Gvili A, Paul M, et al. Immunoglobulin prophylaxis in hematopoietic stem cell transplantation: systematic review and meta-analysis[J]. J Clin Oncol,2009,27(5):770-781.

Please choose a citation manager

Content to export