CD45分子在HIV-1病毒感染中的作用研究進(jìn)展

李克雷，薛 婧，魏 強(qiáng)

(北京協(xié)和醫(yī)學(xué)院比較醫(yī)學(xué)中心，中國(guó)醫(yī)學(xué)科學(xué)院醫(yī)學(xué)實(shí)驗(yàn)動(dòng)物研究所，衛(wèi)生部人類疾病比較醫(yī)學(xué)重點(diǎn)實(shí)驗(yàn)室，國(guó)家中醫(yī)藥管理局人類疾病動(dòng)物模型三級(jí)實(shí)驗(yàn)室，新發(fā)再發(fā)傳染病動(dòng)物模型研究北京市重點(diǎn)實(shí)驗(yàn)室，北京 100021)

CD45分子在HIV-1病毒感染中的作用研究進(jìn)展

李克雷，薛 婧，魏 強(qiáng)

(北京協(xié)和醫(yī)學(xué)院比較醫(yī)學(xué)中心，中國(guó)醫(yī)學(xué)科學(xué)院醫(yī)學(xué)實(shí)驗(yàn)動(dòng)物研究所，衛(wèi)生部人類疾病比較醫(yī)學(xué)重點(diǎn)實(shí)驗(yàn)室，國(guó)家中醫(yī)藥管理局人類疾病動(dòng)物模型三級(jí)實(shí)驗(yàn)室，新發(fā)再發(fā)傳染病動(dòng)物模型研究北京市重點(diǎn)實(shí)驗(yàn)室，北京 100021)

CD45分子是具有磷酸酶活性的跨膜蛋白，在免疫細(xì)胞中發(fā)揮重要作用。CD45分子對(duì)抗原受體信號(hào)轉(zhuǎn)導(dǎo)是必需的，并具有調(diào)節(jié)細(xì)胞凋亡的作用，其功能紊亂會(huì)導(dǎo)致自身免疫性疾病、免疫缺陷、惡性腫瘤等。CD45分子的結(jié)構(gòu)及其功能與HIV感染之間的關(guān)系是艾滋病研究領(lǐng)域的重要內(nèi)容之一，本文就CD45分子在HIV感染中的作用作一綜述。

CD45；HIV；免疫細(xì)胞

CD45分子是受體蛋白酪氨酸磷酸酶，主要表達(dá)于有核的造血細(xì)胞，主要功能涉及造血細(xì)胞的發(fā)育、活化、衰老和凋亡。CD45對(duì)T細(xì)胞的發(fā)育非常重要，如果CD45丟失，那么在胸腺中進(jìn)行的雙陽(yáng)性選擇會(huì)導(dǎo)致細(xì)胞的大量凋亡。此外，CD45作為跨膜分子，在細(xì)胞的信號(hào)轉(zhuǎn)導(dǎo)中發(fā)揮重要作用。鑒于CD45是細(xì)胞膜上信號(hào)轉(zhuǎn)導(dǎo)的關(guān)鍵分子，在淋巴細(xì)胞的發(fā)育成熟、功能調(diào)節(jié)及信號(hào)傳遞中具有重要意義。

1 CD45分子的結(jié)構(gòu)

CD45分子為I型跨膜糖蛋白，其胞內(nèi)區(qū)由D1、D2兩個(gè)結(jié)構(gòu)域組成，D1結(jié)構(gòu)域具有酪氨酸磷酸酶活性，D2結(jié)構(gòu)域?qū)1結(jié)構(gòu)域的活性起調(diào)節(jié)作用；其胞外區(qū)包括3個(gè)纖維連接蛋白區(qū)、1個(gè)半胱氨酸富集區(qū)和3個(gè)由mRNA的選擇性剪接得到的結(jié)構(gòu)域，即A、B、C異構(gòu)體。成熟的CD45分子量范圍為180—240 kDa，其最大的異構(gòu)體為CD45RABC，最小的變構(gòu)體為CD45RO，結(jié)構(gòu)如圖1所示[1]。CD45RABC富含O-聚糖和N-聚糖，主要包括A、B、C 3個(gè)含O-聚糖的區(qū)域，近膜端區(qū)域含有N-聚糖；另一種剪接形式CD45RO僅含有N-聚糖的近膜端區(qū)域，不含有O-聚糖。

CD45分子上的O-聚糖主要包括兩個(gè)核心結(jié)構(gòu)：core-1與core-2[2]，這兩個(gè)核心結(jié)構(gòu)可被聚N-乙?；?、唾液酸和海藻糖修飾。與O-聚糖不同，N-聚糖前體合成時(shí)具有甘露糖結(jié)構(gòu)，以便其在高爾基體內(nèi)修飾，N-聚糖的這種結(jié)構(gòu)增加了CD45的穩(wěn)定性。糖基化形式在細(xì)胞表面的變化對(duì)細(xì)胞存活及功能具有重要影響。

圖1 CD45分子結(jié)構(gòu)示意圖 [19]Fig.1 Schematic diagram of the molecular structure of CD45

2 CD45分子在免疫細(xì)胞中的作用

CD45分子是T細(xì)胞活化所必需的。研究表明TCR或CD3信號(hào)刺激不能使CD45表達(dá)缺失的T細(xì)胞增殖和產(chǎn)生細(xì)胞因子[3、4]，并且在CD45缺陷的小鼠模型中也證明CD45在免疫系統(tǒng)中發(fā)揮的重要作用[5、6]。

CD45分子主要是通過(guò)蛋白酪氨酸激酶(PTKs)的調(diào)節(jié)來(lái)實(shí)現(xiàn)對(duì)淋巴細(xì)胞的發(fā)育和活化的調(diào)控[7]。PTKs由Src家族(p56lck和p59fyn)、Syr家族(ZAP-70)和Jak家族組成，CD45對(duì)p56lck和p59fyn的調(diào)節(jié)在淋巴細(xì)胞活化和信號(hào)轉(zhuǎn)導(dǎo)中起重要作用。p56lck和p59fyn分子結(jié)構(gòu)上存在兩個(gè)關(guān)鍵的調(diào)節(jié)性酪氨酸磷酸化位點(diǎn)，即一個(gè)活化位點(diǎn)和一個(gè)抑制位點(diǎn)。CD45通過(guò)使活化位點(diǎn)和抑制位點(diǎn)去磷酸化控制Src激酶的活性[8]。在靜息淋巴細(xì)胞中，CD45可以和磷酸基團(tuán)競(jìng)爭(zhēng)抑制位點(diǎn)并使活化位點(diǎn)去磷酸化，使Src激酶處于非活化狀態(tài)。當(dāng)抗原和受體結(jié)合后，膜蛋白的位置發(fā)生改變，Src激酶向抗原受體方向位移，使Src激酶和CD45分離，活化位點(diǎn)磷酸化而使Src激酶活化，此時(shí)CD45發(fā)揮正向調(diào)節(jié)作用。在整合素介導(dǎo)的細(xì)胞粘附過(guò)程中，Src激酶和CD45同時(shí)向粘附位點(diǎn)位移，活化位點(diǎn)去磷酸化，此時(shí)CD45發(fā)揮負(fù)調(diào)節(jié)作用[9、10]。

在淋巴T細(xì)胞的分化過(guò)程中，CD45表達(dá)不同的異構(gòu)體，同時(shí)細(xì)胞表面的糖基化也發(fā)生改變。T細(xì)胞表面的糖基化形式可用來(lái)區(qū)分T細(xì)胞亞群[11]，花生凝集素可與無(wú)唾液酸化的core-1O-聚糖結(jié)合，而不能與唾液酸化core-1O-聚糖結(jié)合，而兩者在不同細(xì)胞上存在，前者存在于活化T細(xì)胞，后者存在于初始T細(xì)胞。Core-2O-聚糖存在于不成熟的胸腺細(xì)胞，而不存在于成熟的胸腺細(xì)胞，也存在于活化的T細(xì)胞而非初始T細(xì)胞[12、13]。CD45糖基化對(duì)細(xì)胞的功能及存活可產(chǎn)生重要影響。CD45糖基化可調(diào)節(jié)T細(xì)胞的細(xì)胞因子產(chǎn)生[14]，凝集素jacalin可通過(guò)特異地與CD45 core-1O-聚糖末端的Galβ1-3GalNAc結(jié)合而活化T細(xì)胞，并誘導(dǎo)T細(xì)胞產(chǎn)生IL-2。Galectin-1也可通過(guò)與CD45的結(jié)合調(diào)節(jié)細(xì)胞因子的產(chǎn)生，減少Th1的細(xì)胞因子水平，增加Th2細(xì)胞因子的產(chǎn)生能力[15、16]；CD45糖基化對(duì)調(diào)節(jié)細(xì)胞凋亡的易感性，galectin-1結(jié)合CD45誘導(dǎo)T細(xì)胞凋亡，只有當(dāng)T細(xì)胞共表達(dá)C2GnT和CD45的core-2O-聚糖時(shí)，galectin-1才能誘導(dǎo)凋亡[17、18]。Galectin-3也可誘導(dǎo)T細(xì)胞凋亡，而這一過(guò)程受到CD45分子O-聚糖和N-聚糖的調(diào)節(jié)，galectin-3能誘導(dǎo)CD45+Jurkat細(xì)胞調(diào)亡，但不能誘導(dǎo)CD45-J45.01細(xì)胞凋亡，galectin-3僅能誘導(dǎo)CD45RABC-J45.01細(xì)胞發(fā)生凋亡卻不能誘導(dǎo)CD45RO-J45.01細(xì)胞發(fā)生凋亡，表明CD45分子中的O-聚糖在調(diào)節(jié)galectin-3誘導(dǎo)Jurkat細(xì)胞調(diào)亡中發(fā)揮著重要的作用[19]。

3 CD45在HIV感染中的作用

T細(xì)胞是HIV感染的主要靶細(xì)胞。在HIV感染時(shí)，對(duì)T細(xì)胞表面分子的變化研究能夠進(jìn)一步闡述HIV的感染機(jī)制。研究表明，表達(dá)CD45RO的CD4+T細(xì)胞更易于結(jié)合HIV-1，而CD45RO-細(xì)胞卻不能結(jié)合[20、21]，并且與HIV在CD4+CD45RABC+初始細(xì)胞內(nèi)復(fù)制程度相比，HIV更容易在CD4+CD45RO+記憶細(xì)胞內(nèi)復(fù)制[22]，當(dāng)HIV感染CD4+CD45RO+細(xì)胞時(shí)，CD3/CD28刺激信號(hào)引起的細(xì)胞核因子反應(yīng)更強(qiáng)烈，進(jìn)一步說(shuō)明HIV在CD45RO+細(xì)胞內(nèi)更易復(fù)制[23]。學(xué)者還發(fā)現(xiàn)HIV感染時(shí)CD45在T細(xì)胞表面的密度減少，CD4+T細(xì)胞上CD45RA和CD45RO表達(dá)降低，CD45RA在CD8+T細(xì)胞上降低，CD45RO在CD8+T細(xì)胞的表達(dá)升高[24、25]，由于CD45基因的多樣性，使得表達(dá)不同CD45分子的細(xì)胞對(duì)病毒的易感性有很大差異。例如將編碼CD45的外顯子進(jìn)行C77G突變后，CD45的mRNA會(huì)發(fā)生異常剪切，最終可增加細(xì)胞對(duì)HIV的易感性[26]；其他研究也顯示CD45的多態(tài)性與細(xì)胞對(duì)HIV的易感性有關(guān)，在非洲烏干達(dá)人中CD45的第4個(gè)外顯子有A54G突變，而這種的突變結(jié)構(gòu)降低了HIV的感染頻率[27]，這些都證明CD45與HIV感染密切相關(guān)。

HIV感染T細(xì)胞后可使細(xì)胞發(fā)生凋亡，多種機(jī)制參與了這一過(guò)程，其中包括CD45分子介導(dǎo)的細(xì)胞凋亡。由于HIV-1感染T細(xì)胞可干擾CD45的酪氨酸磷酸酶活性和PLCγ的功能，對(duì)CD45活性的這種影響與疾病進(jìn)程和細(xì)胞凋亡相關(guān)[28、29]。HIV的Tat、Vpr、Nef、gp120蛋白都可誘導(dǎo)細(xì)胞凋亡[30-33]，但在對(duì)gp120誘導(dǎo)凋亡的研究中發(fā)現(xiàn)，gp120通過(guò)活化誘導(dǎo)的凋亡涉及到了細(xì)胞的活化[30，34]，由于CD45分子在細(xì)胞活化過(guò)程中發(fā)揮重要作用，那么gp120誘導(dǎo)的凋亡可能與CD45有關(guān)。研究表明gp120誘導(dǎo)CD45-的T細(xì)胞凋亡率顯著降低，CD45對(duì)gp120誘導(dǎo)凋亡的是通過(guò)抑制PI3K/Akt途徑誘導(dǎo)FasL表達(dá)實(shí)現(xiàn)的，這表明CD45的胞外區(qū)在調(diào)節(jié)細(xì)胞凋亡過(guò)程中發(fā)揮作用[35]，由于CD45胞外區(qū)具有多種糖基化位點(diǎn)，推測(cè)CD45的糖基化也在調(diào)節(jié)gp120誘導(dǎo)的凋亡過(guò)程中發(fā)揮作用。研究顯示在HIV感染機(jī)體的過(guò)程中，一些未感染的T細(xì)胞的CD45的糖基化修飾發(fā)生變化，即無(wú)唾液酸化core-1O-聚糖和core-2O-聚糖表達(dá)增加，由于這種變化使得這些未感染細(xì)胞而通過(guò)旁觀者效應(yīng)發(fā)生凋亡[36]。

由于HIV潛伏庫(kù)的存在，當(dāng)前的AIDS治療方法并不能有效完全清楚體能的HIV病毒，而潛伏感染的CD4+T是HIV治療的主要障礙[37]。HIV主要潛伏在靜息的記憶T細(xì)胞中[38]，靜息記憶T細(xì)胞表面標(biāo)志為CD4+CD45RO+，故對(duì)CD45分子的深入研究可能為清除HIV潛伏庫(kù)提供新的思路。研究表明，在豬尾獼猴體內(nèi)，表達(dá)于CD4+T細(xì)胞表面的CD45RO 可用于檢測(cè)HIV-1 感染模型中潛伏庫(kù)細(xì)胞的數(shù)量[39]，并且也有學(xué)者采用抗CD45RO的免疫毒素來(lái)清除HIV潛伏庫(kù)細(xì)胞，在體外，該免疫毒素清除潛伏感染細(xì)胞效率可達(dá)到99%，且對(duì)CD45RA+初始T細(xì)胞和CD8+記憶T細(xì)胞無(wú)殺傷作用[40、41]，表明針對(duì)CD45RO的靶向藥物設(shè)計(jì)具有清除HIV潛伏庫(kù)的可行性。

4 展望

CD45是一個(gè)重要的跨膜分子，它以其蛋白酪氨酸磷酸酶活性使蛋白酪氨酸激酶的抑制位點(diǎn)的酪氨酸去磷酸化從而使其活化，進(jìn)而在T細(xì)胞活化的信號(hào)傳遞中起重要作用。隨著對(duì)CD45研究的深入，發(fā)現(xiàn)CD45與多種疾病相關(guān)，人們?cè)噲D利用單克隆抗體或藥物阻斷CD45介導(dǎo)的信號(hào)轉(zhuǎn)導(dǎo)來(lái)阻斷淋巴細(xì)胞的活化，進(jìn)而應(yīng)用于誘導(dǎo)免疫耐受和逆轉(zhuǎn)移植排斥反應(yīng)的研究。但CD45及其結(jié)合蛋白在淋巴細(xì)胞的發(fā)育、增殖和活化過(guò)程中的確切作用機(jī)制仍不甚清楚，特別是CD45分子在HIV感染過(guò)程中的作用以及對(duì)潛伏庫(kù)細(xì)胞形成的作用仍需進(jìn)一步研究。

[1] Dupéré-Minier G, Desharnais P, Bernier J. Involvement of tyrosine phosphatase CD45 in apoptosis [J]. Apoptosis, 2009, 15(1): 1-13.

[2] Furukawa K, Funakoshi Y, Autero M, et al. Structural study of the O-linked sugar chains of human leukocyte tyrosine phosphatase CD45 [J]. Eur J Biochem, 1998, 251(1-2): 288-294.

[3] Pingel JT, Thomas ML. Evidence that the leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation [J]. Cell, 1989, 58(6): 1055-1065.

[4] Koretzky GA, PicusJ, Schultz T, et al. Tyrosine phosphatase CD45 is required for T-cell antigen receptor and CD2-mediated activation of a protein tyrosine kinase and interleukin 2 production [J]. Proc Natl Acad Sci U S A, 1991, 88(6): 2037-2041.

[5] Kishihara K, Penninger J, Wallace VA, et al. Normal B lymphocyte development but impaired T cell maturation in CD45-exon6 protein tyrosine phosphatase-deficient mice.[J]. Cell, 1993, 74(74): 143-156.

[6] Byth KF, Conroy LA, Howlett S, et al. CD45-null transgenic mice reveal a positive regulatory role for CD45 in early thymocyte development, in the selection of CD4+CD8+ thymocytes, and B cell maturation [J]. J Experimenta Med, 2015, 68(1): 105-114.

[7] Penninger JM, Irie-Sasaki J, Sasaki T, et al. CD45: New jobs for an old acquaintance [J]. Nature Immunol, 2001, 2(5): 389-96.

[8] Roach T, Slater S, Koval M, et al. CD45 regulates Src family member kinase activity associated with macrophage integrin-mediated adhesion [J]. Curr Biol, 1997, 7(6): 408-417.

[9] Thomas ML, Brown EJ. Positive and negative regulation of Src-family membrane kinases by CD45 [J]. Immunol Today, 1999, 20(20): 406-411.

[10] Alexander DR. The CD45 tyrosine phosphatase: a positive and negative regulator of immune cell function [J]. Semin Immunol, 2000, 12(4): 349-359.

[11] ReisnerY, Linker-Israeli M, Sharon N. Separation of mouse thymocytes into two subpopulations by the use of peanut agglutinin [J]. Cell Immunol, 2005, 314(7086): 1033-1036.

[12] Galvan M, Murali-Krishna K, Ming LL, et al. Alterations in cell surface carbohydrates on T cells from infected mice can distinguish effector/memory CD8+ T cells from naive cells [J]. J Immunol, 1998, 161(2): 641-648.

[13] Grabie N, Delfs MW, Lim YC, et al. β-Galactoside α2,3-sialyltransferase-I gene expression during Th2 but not Th1 differentiation: implications for core2-glycan formation on cell surface proteins [J]. Eur J Immunol, 2002, 32(10): 2766-2772.

[14] Makoto B, Bruce YM, Motohiro N, et al. Glycosylation-dependent interaction of Jacalin with CD45 induces T lymphocyte activation and Th1/Th2 cytokine secretion [J]. J Leukocyte Biol, 2007, 81(4): 1002-1011.

[15] Cedenolaurent F, Opperman M, Barthel SR, et al. Galectin-1 triggers an immunoregulatory signature in T helper cells functionally defined by il-10 expression[J].J Immunol, 2012,188(7): 3127.

[16] Baum LG, Blackall DP, Sarah AM, et al. Amelioration of graft versus host disease by galectin-1 [J]. Clin Immunol, 2003, 109(3): 295-307.

[17] Nguyen JT, Evans DP, Galvan M, et al. CD45 modulates galectin-1-induced T cell death: regulation by expression of core 2 O-glycans [J]. J Immunol, 2001, 167(10): 5697-707.

[18] Galvan M, Tsuboi S, Fukuda M, et al. Expression of a specific glycosyltransferase enzyme regulates T cell death mediated by galectin-1 [J]. J Biol Chem, 2000, 275(22): 16730-16737.

[19] Jing X, Xiqiang G, Chunyan F, et al. Regulation of galectin-3-induced apoptosis of Jurkat cells by both O-glycans and N-glycans on CD45 [J]. FEBS Letters, 2013, 587(24): 3986-3994.

[20] Julià B, Jordi B, Arantxa G, et al. Preferential attachment of HIV particles to activated and CD45RO+CD4+T cells [J]. AIDS Res Human Retroviruses, 2002, 18(1): 27-38.

[21] WangWF, Guo J, Yu DY, et al. A dichotomy in cortical actin and chemotactic actin activity between human memory and naive T cells contributes to their differential susceptibility to HIV-1 infection [J]. J Biol Chem, 2012, 287(42): 35455-35469

[22] Spina CA, Prince HE, Richman DD. Preferential replication of HIV-1 in the CD45RO memory cell subset of primary CD4 lymphocytes in vitro [J]. J Clin Invest, 1997, 99(7): 1774-1785

[23] Robichaud G A, Benoit B, Jean-Francois F, et al. Nuclear factor of activated T cells is a driving force for preferential productive HIV-1 infection of CD45RO-expressing CD4+ T cells [J]. J Biol Chem, 2002, 277(26): 23733-13741.

[24] Mahalingam M, Pozniak A, Mcmanus T J, et al. Abnormalities of CD45 isoform expression in HIV infection [J]. Clin Immunol Immunopathol, 1996, 81(2): 210-214.

[25] Bruunsgaard H, Pedersen C, Scheibel E, et al. Increase in percentage of CD45RO+/CD8+ cells is associated with previous severe primary HIV infection [J]. J Acquired Immune Defic Syndr Human Retrovirol, 1995, 10(2): 107-114.

[26] Tchilian EZ, Wallace DL, Dawes R, et al. A point mutation in CD45 may be associated with an increased risk of HIV-1 infection [J]. AIDS, 2001, 15(15): 1892-1894

[27] Stanton T, Boxall S, Bennett A, et al. CD45 variant alleles: possibly increased frequency of a novel exon 4 CD45 polymorphism in HIV seropositive Ugandans [J]. Immunogenetics, 2004, 56(2): 107-110.

[28] Giovannetti A, Pierdominici M, Mazzetta F, et al. HIV type 1-induced inhibition of CD45 tyrosine phosphatase activity correlates with disease progression and apoptosis, but not with anti-CD3-induced T cell proliferation [J]. AIDS Res Human Retroviruses, 2000, 16(3): 211-219.

[29] Guntermann C, Amft N, Murphy BJ, et al. Impaired CD45-associated tyrosine phosphatase activity during HIV-1 infection: implications for CD3 and CD4 receptor signaling [J]. Biochemical Biophys Res Commun, 1998, 252(1): 69-77.

[30] Roggero R, Robert-Hebmann V, Harrington S, et al. Binding of human immunodeficiency virus type 1 gp120 to CXCR4 induces mitochondrial transmembrane depolarization and cytochrome c-mediated apoptosis independently of Fas signaling [J]. J Virol, 2001, 75(16): 7637-7650.

[31] Lenassi M, Cagney G, Liao M, et al. HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells [J]. Traffic 2010, 11, 110-122.

[32] Nayoung K, Sami K, Sumeet G, et al. Association of Tat with promoters of PTEN and PP2A subunits is key to transcriptional activation of apoptotic pathways in HIV-infected CD4+ T cells [J]. Plos Pathogens, 2010, 6(9): e1001103-e1001103.

[33] Arokium H, Kamata M, Chen I. Virion-associated Vpr of human immunodeficiency virus type 1 triggers activation of apoptotic events and enhances Fas-induced apoptosis in human T cells [J]. J Virol, 2009, 83(21): 11283-11297.

[34] Westendorp MO, Frank R, Ochsenbauer C, et al. Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120 [J]. Nature, 1995, 375(6531): 497-500.

[35] Anand AR, Ganju RK. HIV-1 gp120-mediated apoptosis of T cells is regulated by the membrane tyrosine phosphatase CD45[J]. J Biol Chem, 2006, 281(18): 12289-12299.

[36] Lantéri M, Giordanengo V, Hiraoka N, et al. Altered T cell surface glycosylation in HIV-1 infection results in increased susceptibility to galectin-1-induced cell death [J]. Glycobiology 2003, 13: 909-918.

[37] Dahabieh MS, Battivelli E, Verdin E. Understanding HIV latency: The road to an HIV cure [J]. Ann Rev Med, 2015, 66: 407-421.

[38] Angela C, Pejman M, Monica G, et al. Bioinformatics and HIV latency [J]. Curr HIV/AIDS Rep, 2015, 12(1): 97-106.

[39] Valentine M, Song K, Maresh GA, et al. Expression of the memory marker CD45RO on helper T cells in macaques [J]. PLoS One, 2013, 8(9): e73969.

[40] Mccoig C, Dyke GV, Chou CS, et al. An anti-CD45RO immunotoxin eliminates T cells latently infected with HIV-1 in vitro [J]. Proc Natl Acad Sci U S A, 1999, 96(20): 11482-11485.

[41] Saavedra-Lozano J, Cao Y, Callison J, et al. An anti-CD45RO immunotoxin kills HIV-latently infected cells from individuals on HAART with little effect on CD8 memory [J]. Proc Natl Acad Sci U S A, 2004, 101(8): 2494-2499.

Research progress on the role of CD45 in HIV-1 infection

LI Ke-lei，XUE Jing，WEI Qiang

(Comparative Medicine Center, Peking Union College (PUMC) & Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS); Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing Key Laboratory for Animal Models of Emerging and Re-emerging Infectious Diseases, Beijing 100021, China)

CD45 is a transmembrane molecule with phosphatase activity, and plays a major role in immune cells. CD45 is required for the antigen receptor signal transduction, and attributed as an apoptosis regulator. Impairment of this function may result in autoimmune, immunodeficiency, and malignant diseases. The role of CD45 in HIV-1 infection is one of important research topics. This paper summarizes the research progress on the role of CD45 in HIV-1 infection.

CD45；HIV-1；Immune cells

國(guó)家自然科學(xué)基金(青年科學(xué)基金項(xiàng)目，81301437)，科技部重大專項(xiàng)(2014ZX10001001-001-004，2014ZX10001001-002-006)。

李克雷(1986-)，男，博士生，從事實(shí)驗(yàn)動(dòng)物病毒學(xué)和免疫學(xué)工作。E-mail： leekelei@126.com。

魏強(qiáng)，教授，博士導(dǎo)師，研究方向：實(shí)驗(yàn)動(dòng)物病毒學(xué)。E-mail： weiqiang@cnilas.pumc.edu.cn。

綜述與專論

R-33

A

1671-7856(2017) 06-0082-04

10.3969.j.issn.1671-7856. 2017.06.017

2017-02-21