-
摘要: 获得性免疫缺陷综合征（acquired immune deficiency syndrome，AIDS）是一种由人类免疫缺陷病毒（HIV）引发的全身性疾病。趋化因子配体3[Chemokine （C-C motif） ligand 3，CCL3]作为趋化因子家族的重要成员，在艾滋病发病机制中扮演着不可或缺的角色。CCL3通过阻止HIV进入靶细胞，激活免疫细胞增强抗病毒能力，并调节炎症反应和影响疾病进展，发挥重要的抗病毒和免疫调节作用。大量研究表明CCL3基因拷贝数、特定T细胞反应、CCL3多态性以及其参与的信号通路均影响HIV的发展及病毒载量。综述了CCL3通过阻断HIV-1进入免疫细胞、诱导抗病毒蛋白表达抑制病毒复制，以及其多态性和等位基因对HIV感染及进展的影响等多方面对艾滋病的作用，以期为艾滋病防治策略提供新的理论支撑。Abstract: Acquired immune deficiency syndrome （AIDS） is a systemic disease caused by the Human Immunodeficiency Virus （HIV）. Chemokine （C-C motif） ligand 3 （CCL3）, as a vital member of the chemokine family, plays an indispensable role in the pathogenesis of AIDS. In the context of AIDS, CCL3 exerts significant antiviral and immunomodulatory effects by preventing HIV entry into target cells, activating immune cells to enhance antiviral capabilities, and modulating inflammatory responses, thereby influencing disease progression. Numerous studies have demonstrated that CCL3 gene copy number, specific T-cell responses, CCL3 polymorphisms, and the signaling pathways it participates in all influence the development of HIV and viral load. This article comprehensively reviews the multifaceted roles of CCL3 in AIDS, including its ability to block HIV-1 entry into immune cells, inducing the expression of antiviral proteins to inhibit viral replication, as well as the influence of its polymorphisms and alleles on HIV infection and disease progression, aiming to provide novel theoretical support for AIDS prevention and treatment strategies.
-
[1] Angin M,Sharma S,King M,et al. HIV-1 infection impairs regulatory T-cell suppressive capacity on a per-cell basis[J]. J Infect Dis,2014,210(6):899-903. doi: 10.1093/infdis/jiu188 [2] Sheykhhasan M,Foroutan A,Manoochehri H,et al. Could gene therapy cure HIV?[J]. Life Sci,2021,277:119451. doi: 10.1016/j.lfs.2021.119451 [3] Morty R E,Morris A. World AIDS Day 2021: highlighting the pulmonary complications of HIV/AIDS[J]. Am J Physiol Lung Cell Mol Physiol,2021,321(6):L1069-L1071. doi: 10.1152/ajplung.00471.2021 [4] McEntire C R S,Fong K T,Jia D T,et al. Central nervous system disease with JC virus infection in adults with congenital HIV[J]. Aids,2021,35(2):235-244. doi: 10.1097/QAD.0000000000002734 [5] 热伊拜·亚迪佧尔,陈晶,杨建东,等. 新疆维吾尔自治区2007-2015年HIV/AIDS病例空间自相关分析[J]. 中国艾滋病性病,2017,23(4):292-295. [6] Pang X,Wei H,Huang J,et al. Patterns and risk of HIV-1 transmission network among men who have sex with men in Guangxi,China[J]. Sci Rep,2021,11(1):513. doi: 10.1038/s41598-020-79951-2 [7] 韩孟杰. 我国艾滋病流行形势分析和防治展望[J]. 中国艾滋病性病,2023,29(3):247-250. [8] 刘丽丽,王庆,潘振强. 艾滋病危害宣传的自省式健康教育在艾滋病预防控制中的应用分析[J]. 中国医药指南,2020,18(5):143-144. [9] Aldinucci D,Borghese C,Casagrande N. The CCL5/CCR5 axis in cancer progression[J]. Cancers (Basel),2020,12(7):1765. doi: 10.3390/cancers12071765 [10] Wolpe S D,Davatelis G,Sherry B,et al. Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties[J]. J Exp Med,1988,167(2):570-581. doi: 10.1084/jem.167.2.570 [11] Zlotnik A,Yoshie O. Chemokines: a new classification system and their role in immunity[J]. Immunity,2000,12(2):121-127. doi: 10.1016/S1074-7613(00)80165-X [12] Allen F,Bobanga I D,Rauhe P,et al. CCL3 augments tumor rejection and enhances CD8(+) T cell infiltration through NK and CD103(+) dendritic cell recruitment via IFNγ[J]. Oncoimmunology,2018,7(3):e1393598. doi: 10.1080/2162402X.2017.1393598 [13] Jiao X,Nawab O,Patel T,et al. Recent advances targeting CCR5 for cancer and its role in immuno-oncology[J]. Cancer Res,2019,79(19):4801-4807. doi: 10.1158/0008-5472.CAN-19-1167 [14] Xu X Q,Guo L,Wang X,et al. Human cervical epithelial ccells release antiviral factors and inhibit HIV replication in macrophages[J]. J Innate Immun,2019,11(1):29-40. doi: 10.1159/000490586 [15] Ao Z,Wang L,Azizi H,et al. Development and evaluation of an ebola virus glycoprotein mucin-like domain replacement system as a new dendritic cell-targeting vaccine approach against HIV-1[J]. J Virol,2021,95(15):e0236820. doi: 10.1128/JVI.02368-20 [16] Yin X,Wang Z,Wu T,et al. The combination of CXCL9,CXCL10 and CXCL11 levels during primary HIV infection predicts HIV disease progression[J]. J Transl Med,2019,17(1):417. doi: 10.1186/s12967-019-02172-3 [17] Christo P P,Vilela Mde C,Bretas T L,et al. Cerebrospinal fluid levels of chemokines in HIV infected patients with and without opportunistic infection of the central nervous system[J]. J Neurol Sci,2009,287(1-2):79-83. doi: 10.1016/j.jns.2009.09.002 [18] Jennes W,Sawadogo S,Koblavi-Dème S,et al. Positive association between beta-chemokine-producing T cells and HIV type 1 viral load in HIV-infected subjects in Abidjan,Côte d'Ivoire[J]. AIDS Res Hum Retroviruses,2002,18(3):171-177. doi: 10.1089/08892220252781220 [19] Wright S M,Mleczko A,Coats K S. Bovine immunodeficiency virus expression in vitro is reduced in the presence of beta-chemokines,MIP-1alpha,MIP-1beta and RANTES[J]. Vet Res Commun,2002,26(3):239-250. doi: 10.1023/A:1015209806058 [20] Meddows-Taylor S,Donninger S L,Paximadis M,et al. Reduced ability of newborns to produce CCL3 is associated with increased susceptibility to perinatal human immunodeficiency virus 1 transmission[J]. J Gen Virol,2006,87(Pt 7): 2055-2065. [21] Petkov S,Chiodi F. Distinct transcriptomic profiles of naïve CD4+ T cells distinguish HIV-1 infected patients initiating antiretroviral therapy at acute or chronic phase of infection[J]. Genomics,2021,113(6):3487-3500. doi: 10.1016/j.ygeno.2021.08.014 [22] Vega J A,Villegas-Ospina S,Aguilar-Jiménez W,et al. Haplotypes in CCR5-CCR2,CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort[J]. Biomedica,2017,37(2):267-273. [23] Paximadis M,Schramm D B,Gray G E,et al. Influence of intragenic CCL3 haplotypes and CCL3L copy number in HIV-1 infection in a sub-Saharan African population[J]. Genes Immun,2013,14(1):42-51. doi: 10.1038/gene.2012.51 [24] Shalekoff S,Meddows-Taylor S,Schramm D B,et al. Host CCL3L1 gene copy number in relation to HIV-1-specific CD4+ and CD8+ T-cell responses and viral load in South African women[J]. J Acquir Immune Defic Syndr,2008,48(3):245-254. doi: 10.1097/QAI.0b013e31816fdc77 [25] Lim S Y,Chan T,Gelman R S,et al. Contributions of Mamu-A*01 status and TRIM5 allele expression,but not CCL3L copy number variation,to the control of SIVmac251 replication in Indian-origin rhesus monkeys[J]. PLoS Genet,2010,6(6):e1000997. doi: 10.1371/journal.pgen.1000997 [26] Gonzalez E,Kulkarni H,Bolivar H,et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility[J]. Science,2005,307(5714):1434-1440. doi: 10.1126/science.1101160 [27] Hu L,Song W,Brill I,et al. Genetic variations and heterosexual HIV-1 infection: Analysis of clustered genes encoding CC-motif chemokine ligands[J]. Genes Immun,2012,13(2):202-205. doi: 10.1038/gene.2011.70 [28] Gonzalez E,Dhanda R,Bamshad M,et al. Global survey of genetic variation in CCR5,RANTES,and MIP-1alpha: impact on the epidemiology of the HIV-1 pandemic[J]. Proc Natl Acad Sci U S A,2001,98(9):5199-5204. doi: 10.1073/pnas.091056898 [29] Modi W S,Lautenberger J,An P,et al. Genetic variation in the CCL18-CCL3-CCL4 chemokine gene cluster influences HIV Type 1 transmission and AIDS disease progression[J]. Am J Hum Genet,2006,79(1):120-128. doi: 10.1086/505331 [30] 靳廷丽,刘丽萍,易志强,等. 江西人群CCL3L1基因拷贝数与HIV感染相关性研究[J]. 实验与检验医学,2017,35(02):163-166. doi: 10.3969/j.issn.1674-1129.2017.02.008 [31] Casazza J P,Brenchley J M,Hill B J,et al. Autocrine production of beta-chemokines protects CMV-Specific CD4 T cells from HIV infection[J]. PLoS Pathog,2009,5(10):e1000646. doi: 10.1371/journal.ppat.1000646 [32] Walker W E,Kurscheid S,Joshi S,et al. Increased Levels of Macrophage Inflammatory Proteins Result in Resistance to R5-Tropic HIV-1 in a Subset of Elite Controllers[J]. J Virol,2015,89(10):5502-5514. doi: 10.1128/JVI.00118-15 [33] Hudspeth K,Fogli M,Correia D V,et al. Engagement of NKp30 on Vδ1 T cells induces the production of CCL3,CCL4,and CCL5 and suppresses HIV-1 replication[J]. Blood,2012,119(17):4013-4016. doi: 10.1182/blood-2011-11-390153 [34] Zhou L,Wang X,Xiao Q,et al. Flagellin restricts HIV-1 infection of macrophages through modulation of viral entry receptors and CC chemokines[J]. Viruses,2024,16(7):1063. doi: 10.3390/v16071063 [35] Phetsouphanh C,Phalora P,Hackstein C P,et al. Human MAIT cells respond to and suppress HIV-1[J]. Elife,2021,10:e50324. doi: 10.7554/eLife.50324 [36] Ellegard R,Crisci E,Andersson J,et al. Impaired NK cell activation and chemotaxis toward dendritic cells exposed to complement-opsonized HIV-1[J]. J Immunol,2015,195(4):1698-1704. doi: 10.4049/jimmunol.1500618 [37] Flórez-Álvarez L,Hernandez J C,Zapata W. NK cells in HIV-1 infection: from basic science to vaccine strategies[J]. Front Immunol,2018,9:2290. doi: 10.3389/fimmu.2018.02290 [38] Furtado Milão J,Love L,Gourgi G,et al. Natural killer cells induce HIV-1 latency reversal after treatment with pan-caspase inhibitors[J]. Front Immunol,2022,13:1067767. doi: 10.3389/fimmu.2022.1067767 [39] Rossi F W,Prevete N,Rivellese F,et al. HIV-1 Nef promotes migration and chemokine synthesis of human basophils and mast cells through the interaction with CXCR4[J]. Clin Mol Allergy,2016,14:15. doi: 10.1186/s12948-016-0052-1 [40] Dai M,Wang X,Li J L,et al. Activation of TLR3/interferon signaling pathway by bluetongue virus results in HIV inhibition in macrophages[J]. Faseb j,2015,29(12):4978-4988. doi: 10.1096/fj.15-273128 [41] Temerozo J R,Joaquim R,Regis E G,et al. Macrophage resistance to HIV-1 infection is enhanced by the neuropeptides VIP and PACAP[J]. PLoS One,2013,8(6):e67701. doi: 10.1371/journal.pone.0067701 [42] Gornalusse G G,Valdez R,Fenkart G,et al. Mechanisms of endogenous HIV-1 reactivation by endocervical epithelial cells[J]. J Virol,2020,94(9):e01904-e01919. [43] Shang L,Duan L,Perkey K E,et al. Epithelium-innate immune cell axis in mucosal responses to SIV[J]. Mucosal Immunol,2017,10(2):508-519. doi: 10.1038/mi.2016.62 [44] Coelho A V C,Gratton R,Melo J P B,et al. HIV-1 infection transcriptomics: Meta-Analysis of CD4+ T cells gene expression profiles[J]. Viruses,2021,13(2):244. doi: 10.3390/v13020244 [45] Sun B,da Costa K A S,Alrubayyi A,et al. HIV/HBV coinfection remodels the immune landscape and natural killer cell ADCC functional responses[J]. Hepatology,2024,80(3):649-663. doi: 10.1097/HEP.0000000000000877 [46] Fisher B S,Green R R,Brown R R,et al. Liver macrophage-associated inflammation correlates with SIV burden and is substantially reduced following cART[J]. PLoS Pathog,2018,14(2):e1006871. doi: 10.1371/journal.ppat.1006871 [47] Roscic-Mrkic B,Fischer M,Leemann C,et al. RANTES (CCL5) uses the proteoglycan CD44 as an auxiliary receptor to mediate cellular activation signals and HIV-1 enhancement[J]. Blood,2003,102(4):1169-1177. doi: 10.1182/blood-2003-02-0488 [48] Del Corno M,Liu Q H,Schols D,et al. HIV-1 gp120 and chemokine activation of Pyk2 and mitogen-activated protein kinases in primary macrophages mediated by calcium-dependent,pertussis toxin-insensitive chemokine receptor signaling[J]. Blood,2001,98(10):2909-2916. doi: 10.1182/blood.V98.10.2909 [49] Zhang R Z,Kane M. Insights into the role of HIV-1 Vpu in modulation of NF-ĸB signaling pathways[J]. mBio,2023,14(4):e0092023. [50] Wang H,Liu Y,Huan C,et al. NF-κB-interacting long noncoding RNA regulates HIV-1 replication and latency by repressing NF-κB signaling[J]. J Virol,2020,94(17):e01057-20. [51] Chan J K,Greene W C. NF-κB/Rel: Agonist and antagonist roles in HIV-1 latency[J]. Curr Opin HIV AIDS,2011,6(1):12-18. doi: 10.1097/COH.0b013e32834124fd [52] O'Connell P,Pepelyayeva Y,Blake M K,et al. SLAMF7 is a critical negative regulator of IFN-α-mediated CXCL10 production in chronic HIV infection[J]. J Immunol,2019,202(1):228-238. doi: 10.4049/jimmunol.1800847 [53] Sturt A S,Webb E L,Patterson C,et al. Cervicovaginal immune activation in zambian women with female genital schistosomiasis[J]. Front Immunol,2021,12:620657. doi: 10.3389/fimmu.2021.620657 [54] Chen J,He Y,Zhong H,et al. Transcriptome analysis of CD4(+) T cells from HIV-infected individuals receiving ART with LLV revealed novel transcription factors regulating HIV-1 promoter activity[J]. Virol Sin,2023,38(3):398-408. doi: 10.1016/j.virs.2023.03.001 [55] Blondin-Ladrie L,Fourcade L,Modica A,et al. Monocyte gene and molecular expression profiles suggest distinct effector and regulatory functions in beninese HIV highly exposed seronegative female commercial sex workers[J]. Viruses,2022,14(2):361. doi: 10.3390/v14020361 [56] Vanpouille C,Wells A,Wilkin T,et al. Sex differences in cytokine profiles during suppressive antiretroviral therapy[J]. Aids,2022,36(9):1215-1222. [57] Ao Z,Wang L,Mendoza E J,et al. Incorporation of ebola glycoprotein into HIV particles facilitates dendritic cell and macrophage targeting and enhances HIV-specific immune responses[J]. PLoS One,2019,14(5):e0216949. doi: 10.1371/journal.pone.0216949 [58] Hunegnaw R,Helmold Hait S,Enyindah-Asonye G,et al. A mucosal adenovirus prime/systemic envelope boost vaccine regimen elicits responses in cervicovaginal and alveolar macrophages of rhesus macaques associated with delayed SIV acquisition and B cell help[J]. Front Immunol,2020,11:571804. doi: 10.3389/fimmu.2020.571804 [59] Ka'e A C,Nanfack A J,Ambada G,et al. Inflammatory profile of vertically HIV-1 infected adolescents receiving ART in cameroon: A contribution toward optimal pediatric HIV control strategies[J]. Front Immunol,2023,14:1239877. doi: 10.3389/fimmu.2023.1239877 [60] Petkov S,Herrera C,Else L,et al. Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa[J]. Front Immunol,2022,13:965214. doi: 10.3389/fimmu.2022.965214 -
下载:
点击查看大图
图(1)
计量
- 文章访问数: 56
- HTML全文浏览量: 24
- PDF下载量: 1
- 被引次数: 0
