TRIM22抗HIV-1作用机制研究进展

doi:10.3760/cma.j.cn441417-20240805-04008

摘要/Abstract

摘要：

人类免疫缺陷病毒1型（human immunodeficiency virus-1，HIV-1）对靶细胞的感染受到宿主细胞蛋白的限制，其中三基序蛋白（tripartite-motif protein，TRIM）家族是具有抗病毒作用和调节固有免疫反应的限制因子。TRIM22作为TRIM家族的一员，可被干扰素强烈上调，已被证明在抗HIV-1过程中发挥着重要作用，可通过调节自噬信号通路或转录因子特异蛋白1（specific protein 1，Sp1）来抑制病毒的复制及转录过程。本文主要阐述TRIM22结构、细胞定位及其抗HIV-1的作用机制，以期为HIV-1防治提供理论依据。

关键词:

人类免疫缺陷病毒1型, 干扰素, 三基序蛋白22, 自噬, 特异蛋白1, 进展

Abstract:

The infection of target cells by human immunodeficiency virus-1 (HIV-1) is limited by hosts' cell proteins; among which, the tripartite motif protein (TRIM) family is an important limiting factor with antiviral effects and regulation of innate immune responses. TRIM22, as a member of the TRIM family, can be strongly upregulated by interferon, and has been shown to play an important role in the anti-HIV-1 process. It can inhibit virus replication and transcription regulating the autophagy signaling pathway or transcription factor specific protein 1 (Sp1). This article mainly elaborates the structure, cellular localization, and mechanisms of TRIM22 in combating HIV-1, so as to provide theoretical basis for HIV-1 prevention and treatment.

Key words:

Human immunodeficiency virus-1, Interferon, Tripartite motif protein 22, Autophagy, Specific protein 1, Progress

张子怡孙大康.

TRIM22抗HIV-1作用机制研究进展 [J]. 国际医药卫生导报, 2025, 31(6): 918-922.

Zhang Ziyi, Sun Dakang.

Research progress on mechanism of TRIM22 against HIV-1 [J]. International Medicine and Health Guidance News, 2025, 31(6): 918-922.

参考文献

[1] Williams E, Moso M, Lim C, et al. Laboratory diagnosis of HIV: a contemporary overview in the Australian context[J]. Pathology, 2023,55(5):610-620. DOI: 10.1016/j.pathol.2023.04.001.
[2] Gaikwad SY, Phatak P, Mukherjee A. Cutting edge strategies for screening of novel anti-HIV drug candidates against HIV infection: a concise overview of cell based assays [J]. Heliyon, 2023, 9(5): e16027. DOI: 10.1016/j.heliyon.2023.e16027.
[3] Landovitz RJ, Scott H, Deeks SG. Prevention, treatment and cure of HIV infection[J]. Nat Rev Microbiol, 2023, 21(10): 657-670. DOI: 10.1038/s41579-023-00914-1.
[4] Madham S, Visshishta J, Dasagari VH, et al. A review of basic knowledge of hiv infection for orthodontic management of HIV patients[J]. Cureus, 2023, 15(4): e37770. DOI: 10.7759/cureus.37770.
[5] Koepke L, Gack MU, Sparrer KM. The antiviral activities of TRIM proteins [J]. Curr Opin Microbiol, 2021, 59: 50-57. DOI: 10.1016/j.mib.2020.07.005.
[6] Di Rienzo M, Romagnoli A, Antonioli M, et al. TRIM proteins in autophagy: selective sensors in cell damage and innate immune responses [J]. Cell Death Differ, 2020,27(3): 887-902. DOI: 10.1038/s41418-020-0495-2.
[7] Tao T, Zhang Y, Guan C, et al. Ubiquitin ligase TRIM22 inhibits ovarian cancer malignancy via TCF4 degradation[J]. Mol Cancer Res, 2024. DOI: 10.1158/1541-7786.MCR-23-0962.
[8] Eldin P, Papon L, Oteiza A, et al. TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral activity against encephalomyocarditis virus[J]. J Gen Virol, 2009, 90(Pt 3): 536-545. DOI: 10.1099/vir.0.006288-0.
[9] Lorick KL, Jensen JP, Fang S, et al. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination[J]. Proc Natl Acad Sci U S A, 1999,96(20):11364-11369. DOI: 10.1073/pnas.96.20.11364.
[10] Buetow L, Huang DT. Structural insights into the catalysis and regulation of E3 ubiquitin ligases [J]. Nat Rev Mol Cell Biol, 2016,17(10): 626-642. DOI: 10.1038/nrm.2016.91.
[11] Jia X, Zhao Q, Xiong Y. HIV suppression by host restriction factors and viral immune evasion[J]. Curr Opin Struct Biol, 2015, 31: 106-114. DOI: 10.1016/j.sbi.2015.04.004.
[12] Wu X, Anderson JL, Campbell EM, et al. Proteasome inhibitors uncouple rhesus TRIM5alpha restriction of HIV-1 reverse transcription and infection[J]. Proc Natl Acad Sci U S A, 2006, 103(19): 7465-7470. DOI: 10.1073/pnas.0510483103.
[13] Li X, Yeung DF, Fiegen AM, et al. Determinants of the higher order association of the restriction factor TRIM5alpha and other tripartite motif (TRIM) proteins[J]. J Biol Chem, 2011, 286(32): 27959-27970. DOI: 10.1074/jbc.M111.260406.
[14] Sivaramakrishnan G, Sun Y, Rajmohan R, et al. B30.2/SPRY domain in tripartite motif-containing 22 is essential for the formation of distinct nuclear bodies [J]. FEBS Lett, 2009, 583(12): 2093-2099. DOI: 10.1016/j.febslet.2009.05.036.
[15] Esposito D, Koliopoulos MG, Rittinger K. Structural determinants of TRIM protein function[J]. Biochem Soc Trans, 2017, 45(1): 183-191. DOI: 10.1042/BST20160325.
[16] Rhodes D A, de Bono B, Trowsdale J. Relationship between SPRY and B30.2 protein domains. Evolution of a component of immune defence? [J]. Immunology, 2005, 116(4): 411-417. DOI: 10.1111/j.1365-2567. 2005.02248.x.
[17] Grutter C, Briand C, Capitani G, et al. Structure of the PRYSPRY-domain: implications for autoinflammatory diseases[J]. FEBS Lett, 2006, 580(1): 99-106. DOI: 10.1016/j.febslet.2005.11.076.
[18] Yu S, Gao B, Duan Z, et al. Identification of tripartite motif-containing 22 (TRIM22) as a novel NF-kappaB activator[J]. Biochem Biophys Res Commun, 2011, 410(2): 247-251. DOI: 10.1016/j.bbrc.2011.05.124.
[19] Chen C, Zhao D, Fang S, et al. TRIM22-mediated apoptosis is associated with bak oligomerization in monocytes[J]. Sci Rep, 2017,7:39961. DOI: 10.1038/srep39961.
[20] Gao B, Wang Y, Xu W, et al. A 5' extended IFN-stimulating response element is crucial for IFN-gamma-induced tripartite motif 22 expression via interaction with IFN regulatory factor-1[J]. J Immunol, 2010,185(4): 2314-2323. DOI: 10.4049/jimmunol.1001053.
[21] Gao B, Xu W, Zhong L, et al. p300, but not PCAF, collaborates with IRF-1 in stimulating TRIM22 expression independently of its histone acetyltransferase activity[J]. Eur J Immunol, 2013,43(8):2174-2184. DOI: 10.1002/eji.201343308.
[22] Hattlmann CJ, Kelly JN, Barr SD. TRIM22: a diverse and dynamic antiviral protein[J]. Molecular Biology International, 2012:1-10. DOI: 10.1155/2012/153415.
[23] 孙大康, 安新业, 周玉明, 等. HIV衣壳蛋白P24与TRIM22在HEK293T细胞中的表达及共定位[J]. 细胞与分子免疫学杂志, 2015,31(8):1081-1084.
[24] Petersson J, Lonnbro P, Herr AM, et al. The human IFN-inducible p53 target gene TRIM22 colocalizes with the centrosome independently of cell cycle phase[J]. Exp Cell Res, 2010, 316(4): 568-579. DOI: 10.1016/j.yexcr.2009.12.007.
[25] Sivaramakrishnan G, Sun Y, Tan S K, et al. Dynamic localization of tripartite motif-containing 22 in nuclear and nucleolar bodies[J]. Exp Cell Res, 2009,315(8):1521-1532. DOI: 10.1016/j.yexcr.2009.01.028.
[26] Liu S, Yao S, Yang H, et al. Autophagy: regulator of cell death[J]. Cell Death Dis, 2023, 14(10): 648. DOI: 10.1038/s41419-023-06154-8.
[27] Miller DR, Thorburn A. Autophagy and organelle homeostasis in cancer [J]. Dev Cell, 2021, 56(7): 906-918. DOI: 10.1016/j.devcel.2021.02.010.
[28] Matoba K, Noda NN. Structural catalog of core Atg proteins opens new era of autophagy research[J]. J Biochem, 2021,169(5):517-525. DOI: 10.1093/jb/mvab017.
[29] Kumar A V, Mills J, Lapierre LR. Selective autophagy receptor p62/SQSTM1, a pivotal player in stress and aging [J]. Front Cell Dev Biol, 2022, 10: 793328. DOI: 10.3389/fcell.2022.793328.
[30] Espert L, Varbanov M, Robert-Hebmann V, et al. Differential role of autophagy in CD4 T cells and macrophages during X4 and R5 HIV-1 infection [J]. PLoS One, 2009, 4(6): e5787. DOI: 10.1371/journal.pone.0005787.
[31] Kyei GB, Dinkins C, Davis AS, et al. Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages[J]. J Cell Biol, 2009, 186(2): 255-268. DOI: 10.1083/jcb.200903070.
[32] Sagnier S, Daussy CF, Borel S, et al. Autophagy restricts HIV-1 infection by selectively degrading Tat in CD4+ T lymphocytes[J]. J Virol, 2015,89(1): 615-625. DOI: 10.1128/JVI.02174-14.
[33] Cloherty A, Rader AG, Compeer B, et al. Human TRIM5alpha: autophagy connects cell-intrinsic HIV-1 restriction and innate immune sensor functioning[J]. Viruses, 2021,13(2): 320. DOI: 10.3390/v13020320.
[34] Wu N, Gou X, Hu P, et al. Mechanism of autophagy induced by activation of the AMPK/ERK/mTOR signaling pathway after TRIM22-mediated DENV-2 infection of HUVECs [J]. Virol J, 2022, 19(1): 228. DOI: 10.1186/s12985-022-01932-w.
[35] Chen J, Zhao S, Cui Z, et al. MicroRNA-376b-3p promotes porcine reproductive and respiratory syndrome virus replication by targeting viral restriction factor TRIM22[J]. J Virol, 2022, 96(2): e159721. DOI: 10.1128/JVI.01597-21.
[36] Heo H, Park H, Lee M S, et al. TRIM22 facilitates autophagosome-lysosome fusion by mediating the association of GABARAPs and PLEKHM1[J]. Autophagy, 2024, 20(5): 1098-1113. DOI: 10.1080/15548627. 2023.2287925.
[37] Liu W, Zhao Y, Wang G, et al. TRIM22 inhibits osteosarcoma progression through destabilizing NRF2 and thus activation of ROS/AMPK/mTOR/autophagy signaling[J]. Redox Biol, 2022, 53: 102344. DOI: 10.1016/j.redox.2022.102344.
[38] Fields J, Dumaop W, Eleuteri S, et al. HIV-1 Tat alters neuronal autophagy by modulating autophagosome fusion to the lysosome: implications for HIV-associated neurocognitive disorders[J]. The Journal of neuroscience, 2015, 35(5): 1921-1938. DOI: 10.1523/JNEUROSCI. 3207-14.2015.
[39] Van Grol J, Subauste C, Andrade RM, et al. HIV-1 inhibits autophagy in bystander macrophage/monocytic cells through Src-Akt and STAT3[J]. PLoS One, 2010, 5(7): e11733. DOI: 10.1371/journal.pone.0011733.
[40] Espert L. Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4[J]. Journal of Clinical Investigation, 2006, 116(8): 2161-2172. DOI: 10.1172/JCI26185.
[41] Jiang JF, Zhou ZY, Liu YZ, et al. Role of Sp1 in atherosclerosis[J]. Mol Biol Rep, 2022, 49(10): 9893-9902. DOI: 10.1007/s11033-022-07516-9.
[42] Wang P, Song Y, Li H, et al. SIRPA enhances osteosarcoma metastasis by stabilizing SP1 and promoting SLC7A3-mediated arginine uptake[J]. Cancer Lett, 2023, 576: 216412. DOI: 10.1016/j.canlet.2023.216412.
[43] Ivanenko KA, Prassolov VS, Khabusheva ER. Transcription factor Sp1 in the expression of genes encoding components of MAPK, JAK/STAT, and PI3K/Akt signaling pathways [J]. Mol Biol (Mosk), 2022,56(5):832-847. DOI: 10.31857/S0026898422050081.
[44] Nchioua R, Bosso M, Kmiec D, et al. Cellular factors targeting HIV-1 transcription and viral RNA transcripts[J]. Viruses, 2020,12(5): 495. DOI: 10.3390/v12050495.
[45] Kajaste-Rudnitski A, Marelli SS, Pultrone C, et al. TRIM22 inhibits HIV-1 transcription independently of its E3 ubiquitin ligase activity, Tat, and NF-kappaB-responsive long terminal repeat elements [J]. J Virol, 2011,85(10): 5183-5196. DOI: 10.1128/JVI.02302-10.
[46] Turrini F, Marelli S, Kajaste-Rudnitski A, et al. HIV-1 transcriptional silencing caused by TRIM22 inhibition of Sp1 binding to the viral promoter[J]. Retrovirology, 2015,12(104):104. DOI: 10.1186/s12977-015-0230-0.
[47] Turrini F, Saliu F, Forlani G, et al. Interferon-inducible TRIM22 contributes to maintenance of HIV-1 proviral latency in T cell lines[J]. Virus Res, 2019, 269: 197631. DOI: 10.1016/j.virusres.2019.05.009.
[48] Butovskaya E, Heddi B, Bakalar B, et al. Major G-quadruplex form of HIV-1 LTR reveals a (3 + 1) folding topology containing a stem-loop[J]. J Am Chem Soc, 2018,140(42): 13654-13662. DOI: 10.1021/jacs.8b05332.
[49] Rohr O, Aunis D, Schaeffer E. COUP-TF and Sp1 interact and cooperate in the transcriptional activation of the human immunodeficiency virus type 1 long terminal repeat in human microglial cells[J]. J Biol Chem, 1997, 272(49): 31149-31155. DOI: 10.1074/jbc.272.49.31149.