HIV-1感染對(duì)腸粘膜回歸相關(guān)基因表達(dá)影響的實(shí)驗(yàn)研究
發(fā)布時(shí)間：2018-08-12 17:50
【摘要】：目的：HIV-1病毒感染引起粘膜CD4+T細(xì)胞大量缺失,導(dǎo)致粘膜免疫功能損傷、微生物易位及慢性免疫激活,最終導(dǎo)致全身免疫缺陷發(fā)展成為AIDS。雖然感染早期粘膜CD4+T細(xì)胞大量感染,CD4+T淋巴細(xì)胞數(shù)顯著下降,但是外周血CD4+T淋巴細(xì)胞在感染后卻長(zhǎng)期維持在比較高的水平。粘膜CD4+T淋巴細(xì)胞數(shù)量減少的原因目前尚未完全清楚。除了病毒感染直接或間接殺傷CD4+T淋巴細(xì)胞外,淋巴細(xì)胞分布異常也可能是一些組織中CD4+T淋巴細(xì)胞減少的原因。淋巴細(xì)胞循環(huán)是淋巴細(xì)胞向特定組織遷移的過程,由多種分子參與,涉及選擇素家族、整合素家族、免疫球蛋白超家族的粘附分子和多種細(xì)胞因子。對(duì)這些分子在HIV-1感染后的變化尚無系統(tǒng)研究。本研究以SIV/SHIV感染恒河猴為動(dòng)物模型,探索HIV-1對(duì)免疫細(xì)胞回歸相關(guān)基因的影響。 方法：1)提取恒河猴結(jié)腸組織總RNA,利用5'RACE和3'RACE分別擴(kuò)增cDNA序列,將獲得的序列構(gòu)建到pGEM-Teasy載體測(cè)序,利用DNAMan軟件進(jìn)行序列比對(duì)和拼接獲得MAdCAM-1cDNA全序列：從GenBank上獲得40多個(gè)物種MAdCAM-1核苷酸序列,利用BioEidt和MEGA軟件進(jìn)行比對(duì)和構(gòu)建系統(tǒng)進(jìn)化樹。2)根據(jù)天根RNA提取試劑盒說明提取組織RNA、根據(jù)康為世紀(jì)組織蛋白抽提試劑盒說明提取組織蛋白,利用半定量RT-PCR方法和實(shí)時(shí)熒光定量RT-PCR方法檢測(cè)組織中MAdCAM-1mRNA的表達(dá)水平,并用Western Blot方法檢測(cè)了十二指腸活檢組織中MAdCAM-1蛋白的表達(dá)水平。另外利用RT-PCR方法檢測(cè)MAdCAM-1exon4缺失的剪切變異體。3)基因合成恒河猴MAdCAM-1編碼區(qū)全序列(MFL)和第四個(gè)外顯子缺失剪切變異體(ML4),通過酶切連接,構(gòu)建到pCDNA3.1真核表達(dá)載體上,轉(zhuǎn)染293F細(xì)胞,利用流式細(xì)胞術(shù)檢測(cè)細(xì)胞表面MAdCAM-1分子的表達(dá)。將轉(zhuǎn)染后293F細(xì)胞用CFSE染色,Hut-78細(xì)胞用PKH26染色,在Mn2+存在下進(jìn)行粘附實(shí)驗(yàn)。4)選取正常未感染恒河猴和SIV/SHIV感染的Gr4組、SHIV感染的Gr15組和Gr19組恒河猴凍存組織樣本(感染動(dòng)物樣品主要來自本實(shí)驗(yàn)室以往感染實(shí)驗(yàn)的病毒對(duì)照組),按照試劑盒說明提取組織RNA,建立多種基因?qū)崟r(shí)熒光定量RT-PCR檢測(cè)方法,用以檢測(cè)MAdCAM-1、ITGA4、ITGB7、NKX2.3、CCL25、 CCR9、CCL28、CCR10、CCL19、CCL21、CCR7、RGS1、CCL22、CCR4、CCL20、CCR6、 GPR183、FCGRT、PIGR、BCL-6、DDIT3、TNF-α、IFN-γ等23種基因的轉(zhuǎn)錄水平。5)按照康為世紀(jì)組織蛋白抽提試劑盒說明提取四組動(dòng)物組織蛋白,利用Western Blot檢測(cè)MAdCAM-1組織蛋白表達(dá)；利用ELISA檢測(cè)動(dòng)物組織CCL20、TNF-α、IFN-γ、IL-17、IL-6等因子的蛋白表達(dá)水平。 結(jié)果:MAdCAM-1在粘膜特異回歸中具有重要作用。本文首先克隆了恒河猴MAdCAM-1基因,研究了該基因的組織分布與感染后的變化。發(fā)現(xiàn)恒河猴MAdCAM-1cDNA核苷酸序列全長(zhǎng)為1503bp,包括一個(gè)14bp的5’非編碼區(qū)(5'UTR)和一個(gè)403bp的3’非編碼區(qū)(3’UTR),在1463bp位置有一個(gè)AATAAA的多聚加尾信號(hào)。推測(cè)的恒河猴MAdCAM-1蛋白與人MAdCAM-1相似,含有一個(gè)信號(hào)肽,兩個(gè)N端Ig樣結(jié)構(gòu)域,一個(gè)粘蛋白樣結(jié)構(gòu)域,一個(gè)跨膜區(qū)和一個(gè)胞漿區(qū),但是沒有小鼠中的第三個(gè)Ig樣結(jié)構(gòu)域和IgA1樣結(jié)構(gòu)域。與a4β7結(jié)合的LDT保守區(qū)在第一個(gè)Ig樣結(jié)構(gòu)域內(nèi)。 在正常恒河猴組織中,MAdCAM-1mRNA主要表達(dá)于胃腸道、脾和淋巴結(jié)中,在腸系膜淋巴結(jié)中表達(dá)量最高。在腸道中,大腸中表達(dá)量高于小腸。皮膚、胸腺、口腔粘膜和肝臟中MAdCAM-1mRNA的表達(dá)水平很低,其中肝臟中的表達(dá)量最低。在SHIV感染后的十二指腸粘膜組織中,MAdCAM-1的mRNA表達(dá)水平顯著下降,MAdCAM-1蛋白表達(dá)水平也下降。 為進(jìn)一步了解SIV/SHIV感染對(duì)淋巴歸巢相關(guān)基因表達(dá)的影響,本文研究了MAdACM-1及其受體α4β7在正常和感染動(dòng)物腸粘膜中的表達(dá)水平。發(fā)現(xiàn)SIV/SHIV感染后MAdCAM-1mRNA在小腸中下降大腸中上升,同時(shí)MAdCAM-1蛋白.ITGA4、ITGB7和NKX2.3基因表達(dá)也呈現(xiàn)同樣的變化趨勢(shì)。在正常腸粘膜組織中MAdCAM-1、ITGA4、ITGB7的mRNA之間的分布具有相關(guān)性,而MAdCAM-1與NKX2.3之間的分布不具有相關(guān)性,但感染后NKX2.3與MAdCAM-1在腸道分布相關(guān),可能參與MAdCAM-1在腸道的表達(dá)調(diào)控。 更進(jìn)一步研究發(fā)現(xiàn)SIV/SHIV感染也影響了消化道粘膜中多種趨化因子及受體轉(zhuǎn)錄水平。其中,感染后腸道相關(guān)趨化因子CCL25和CCL28及其受體在小腸中呈下降趨勢(shì),而在大腸中呈上升趨勢(shì),不同病毒感染影響也不同。感染后趨化因子CCL19、CCL21和受體CCR7mRNA在淋巴器官?zèng)]有明顯變化,但在十二指腸的表達(dá)顯著下降；趨化因子CCL20mRNA的表達(dá)在感染后沒有顯著變化,而受體CCR6mRNA在十二指腸和空腸顯著下降；感染后趨化因子CCL22mRNA在空腸下降,受體CCR4mRNA在腹股溝淋巴結(jié)中下降。 另外,SIV/SHIV感染也影響細(xì)胞遷移調(diào)節(jié)基因在轉(zhuǎn)錄水平的表達(dá)：GPR183調(diào)節(jié)B細(xì)胞在淋巴濾泡中的遷移,GPRI83mRNA在脾、腸系膜淋巴結(jié)和腹股溝淋巴結(jié)中的表達(dá)顯著降低,RGS1mRNA在胃底和十二指腸的表達(dá)降低。 為了解回歸相關(guān)分子的變化與粘膜中其他免疫病理變化的關(guān)系,本文研究了SIV/SHIV感染后炎癥因子TNF-α、IFN-γ的轉(zhuǎn)錄水平的變化。發(fā)現(xiàn)總體上TNF-α mRNA表達(dá)量在小腸前段下降,從回腸到直腸上升；IFN-γ mRNA在直腸顯著降低,其他部位沒有明顯變化。炎癥因子TNF-α蛋白在空腸和回腸顯著下降,整體上呈現(xiàn)在小腸中下降在大腸中上升的趨勢(shì)；IFN-γ蛋白沒有明顯變化、IL-6蛋白在回腸和盲腸顯著上升、IL-17蛋白在直腸顯著上升。另外還觀察了與IgA轉(zhuǎn)運(yùn)相關(guān)基因轉(zhuǎn)錄水平變化,發(fā)現(xiàn)FCGRT mRNA在腸道粘膜表達(dá)水平上升,而PIGR mRNA在胃腸道和淋巴結(jié)表達(dá)下降,SIV/SHIV感染后BCL-6mRNA在小腸中下降,大腸中上升,而SHIV感染后BCL-6mRNA在胃腸道粘膜(除直腸外)、脾和淋巴結(jié)中均下降。以上結(jié)果表明,SIV/SHIV感染后粘膜體液免疫功能可能受到了影響。 結(jié)論：本研究1)獲得了恒河猴MAdCAM-1cDNA核苷酸序列,發(fā)現(xiàn)與人MAdCAM-1序列高度相似；2)發(fā)現(xiàn)SIV/SHIV感染影響粘膜回歸相關(guān)粘附分子MAdCAM-1與受體α4β7的表達(dá)；3)發(fā)現(xiàn)SIV/SHIV感染影響多種粘膜回歸相關(guān)趨化因子與受體的表達(dá)；4)發(fā)現(xiàn)粘膜回歸相關(guān)因子在SIV/SHIV感染后的變化與粘膜內(nèi)炎癥水平相關(guān)；5)發(fā)現(xiàn)粘膜回歸相關(guān)分子在SIV/SHIV感染后的改變可能伴隨著粘膜體液免疫功能的變化。這些結(jié)果表明HIV-1可能通過影響粘膜淋巴細(xì)胞回歸,進(jìn)而影響粘膜細(xì)胞和體液免疫功能,為深入認(rèn)識(shí)HIV/AIDS病理過程和尋找新的生物學(xué)干預(yù)靶點(diǎn)提供了重要基礎(chǔ)。
[Abstract]:AIM: Mucosal CD4 + T cell deletion, microbial translocation and chronic immune activation caused by HIV-1 virus infection eventually lead to the development of systemic immunodeficiency into AIDS. The cause of the decrease in the number of CD4 + T lymphocytes in the mucosa is not fully understood. In addition to the direct or indirect killing of CD4 + T lymphocytes by virus infection, the abnormal distribution of lymphocytes may also be responsible for the decrease of CD4 + T lymphocytes in some tissues. Lymphocyte circulation is the cause of lymphocyte turnover to specific groups. Tissue migration involves multiple molecules, including selectin family, integrin family, immunoglobulin superfamily adhesion molecules and cytokines. The changes of these molecules after HIV-1 infection have not been systematically studied. Influence.
METHODS: 1) Total RNA was extracted from colon tissue of rhesus monkey, and the sequences were amplified by 5'RACE and 3'RACE respectively. The obtained sequences were constructed into pGEM-Teasy vector and sequenced. The complete sequence of MAdCAM-1 was obtained by DNA Man software. More than 40 species of MAdCAM-1 nucleotide sequences were obtained from GenBank, and BioEidt and MEGA software were used. Comparing and constructing phylogenetic tree.2) Extracting tissue RNA according to Tiangen RNA extraction kit, extracting tissue protein according to Kangwei Century Tissue Protein Extraction kit, using semi-quantitative RT-PCR and real-time fluorescence quantitative RT-PCR to detect the expression of MAdCAM-1 mRNA in tissues, and Western Blot method to detect the expression of MAdCAM-1 mRNA. The expression level of MAdCAM-1 protein in duodenal biopsy tissues was detected by RT-PCR. In addition, the splicing variant of MAdCAM-1 exon 4 deletion was detected by RT-PCR. 3) gene was synthesized into the full sequence of MAdCAM-1 coding region (MFL) and the fourth exon deletion splicing variant (ML4) of rhesus monkey, and then constructed into pCDNA3.1 eukaryotic expression vector by enzyme digestion ligation and transfected 293F fine. After transfection, 293F cells were stained with CFSE, and Hut-78 cells were stained with PKH26. Adhesion test was carried out in the presence of Mn2 +. 4. Gr4, Gr15 and Gr19, which were not infected with SIV / SHIV, were selected as the control group. According to the instructions of the kit, RNA was extracted from the tissues and real-time fluorescence quantitative RT-PCR was used to detect MAdCAM-1, ITGA4, ITGB7, NKX2.3, CCL25, CCR9, CCL28, CCR10, CCL19, CCL21, CCR7, RGS1, CCL22, CCR4, CCL20, CCR6, GPR183, FCGRT, PIGR, BCL-6, DDIT3, CCL21, CCL21, CCR7, CCR7, CCR7, R7, RGS1, CCL22, CCR4, CCL20, CCR6, GPR183, FCGRT, PIGR, BC Transcription levels of 23 genes, such as - alpha, IFN - gamma and so on. 5) According to Kangwei Century Tissue Protein Extraction Kit, four groups of animal tissue proteins were extracted, and the expression of MAdCAM-1 was detected by Western Blot, and the expression levels of CCL20, TNF-alpha, IFN-gamma, IL-17 and IL-6 were detected by ELISA.
Results: MAdCAM-1 plays an important role in mucosa-specific regression. Firstly, the MAdCAM-1 gene of rhesus monkey was cloned and its tissue distribution and changes after infection were studied. The hypothetical MAdCAM-1 protein of rhesus monkey, similar to human MAdCAM-1, contains a signal peptide, two N-terminal Ig-like domains, one mucin-like domain, one transmembrane domain and one cytoplasmic domain, but does not bind to the third Ig-like domain and IgA1-like domain in mice. The conserved region of LDT is in the first Ig like domain.
In normal rhesus monkey tissues, MAdCAM-1 mRNA was mainly expressed in gastrointestinal tract, spleen and lymph nodes, and was the highest in mesenteric lymph nodes. In intestine, the expression level of MAdCAM-1 mRNA was higher in large intestine than in small intestine, skin, thymus, oral mucosa and liver. The expression level of MAdCAM-1 mRNA in liver was the lowest. The expression level of MAdCAM-1 mRNA and MAdCAM-1 protein in intestinal mucosa decreased significantly.
To further understand the effect of SIV/SHIV infection on the expression of lymphatic homing-related genes, the expression of MAdACM-1 and its receptor alpha 4 beta-7 in intestinal mucosa of normal and infected animals was studied. The distribution of MAdCAM-1, ITGA4 and ITGB7 mRNA in normal intestinal mucosa was correlated, but the distribution of MAdCAM-1 and NKX2.3 was not correlated, but NKX2.3 was correlated with the distribution of MAdCAM-1 in intestine after infection, which may be involved in the regulation of MAdCAM-1 expression in intestine.
Further studies showed that SIV/SHIV infection also affected the levels of chemokines and receptors in gastrointestinal mucosa. After infection, intestinal chemokines CCL25, CCL28 and their receptors decreased in the small intestine, but increased in the large intestine, and the effects of different viral infections were different. The expression of chemokine CCL20 mRNA did not change significantly after infection, whereas the expression of chemokine CCR6 mRNA in duodenum and jejunum decreased significantly; the expression of chemokine CCL22 mRNA in jejunum decreased significantly after infection, and the expression of chemokine CCR4 mRNA in inguinal lymph nodes decreased significantly. Drop.
In addition, SIV/SHIV infection also affected the expression of cell migration regulator genes at transcriptional level: GPR183 regulated the migration of B cells in lymphoid follicles, decreased the expression of GPRI83 mRNA in spleen, mesenteric and inguinal lymph nodes, and decreased the expression of RGS1 mRNA in gastric fundus and duodenum.
In order to understand the relationship between the changes of regression-related molecules and other immunopathological changes in mucosa, we studied the changes of the transcription levels of inflammatory factors TNF-a and IFN-gamma after SIV/SHIV infection. Inflammatory factor TNF-alpha protein decreased significantly in jejunum and ileum, but decreased in small intestine and increased in large intestine as a whole; IFN-gamma protein did not change significantly, IL-6 protein increased significantly in ileum and cecum, and IL-17 protein increased significantly in rectum. It was found that FCGRT mRNA increased in intestinal mucosa, PIGR mRNA decreased in gastrointestinal tract and lymph nodes, BCL-6 mRNA decreased in small intestine and increased in large intestine after SIV/SHIV infection, while BCL-6 mRNA decreased in gastrointestinal mucosa (except rectum), spleen and lymph nodes after SHIV infection. The function of the disease may be affected.
CONCLUSIONS: In this study, the sequence of MAdCAM-1 cDNA in rhesus monkeys was obtained and found to be highly similar to that of human MAdCAM-1; 2) SIV/SHIV infection was found to affect the expression of MAdCAM-1 and receptor alpha 4 beta 7; 3) SIV/SHIV infection was found to affect the expression of multiple mucosal regression-related chemokines and receptors; 4) SIV/SHIV infection was found to affect the expression of multiple mucosal regression-related chemokines and receptors These results suggest that HIV-1 may affect mucosal and humoral immune function by influencing mucosal lymphocyte regression, and then influence mucosal cells and humoral immune function. It provides an important basis for understanding the pathological process of HIV/AIDS and finding new biological intervention targets.
【學(xué)位授予單位】：中國(guó)疾病預(yù)防控制中心
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R512.91
，
本文編號(hào)：2179831
[Abstract]:AIM: Mucosal CD4 + T cell deletion, microbial translocation and chronic immune activation caused by HIV-1 virus infection eventually lead to the development of systemic immunodeficiency into AIDS. The cause of the decrease in the number of CD4 + T lymphocytes in the mucosa is not fully understood. In addition to the direct or indirect killing of CD4 + T lymphocytes by virus infection, the abnormal distribution of lymphocytes may also be responsible for the decrease of CD4 + T lymphocytes in some tissues. Lymphocyte circulation is the cause of lymphocyte turnover to specific groups. Tissue migration involves multiple molecules, including selectin family, integrin family, immunoglobulin superfamily adhesion molecules and cytokines. The changes of these molecules after HIV-1 infection have not been systematically studied. Influence.
METHODS: 1) Total RNA was extracted from colon tissue of rhesus monkey, and the sequences were amplified by 5'RACE and 3'RACE respectively. The obtained sequences were constructed into pGEM-Teasy vector and sequenced. The complete sequence of MAdCAM-1 was obtained by DNA Man software. More than 40 species of MAdCAM-1 nucleotide sequences were obtained from GenBank, and BioEidt and MEGA software were used. Comparing and constructing phylogenetic tree.2) Extracting tissue RNA according to Tiangen RNA extraction kit, extracting tissue protein according to Kangwei Century Tissue Protein Extraction kit, using semi-quantitative RT-PCR and real-time fluorescence quantitative RT-PCR to detect the expression of MAdCAM-1 mRNA in tissues, and Western Blot method to detect the expression of MAdCAM-1 mRNA. The expression level of MAdCAM-1 protein in duodenal biopsy tissues was detected by RT-PCR. In addition, the splicing variant of MAdCAM-1 exon 4 deletion was detected by RT-PCR. 3) gene was synthesized into the full sequence of MAdCAM-1 coding region (MFL) and the fourth exon deletion splicing variant (ML4) of rhesus monkey, and then constructed into pCDNA3.1 eukaryotic expression vector by enzyme digestion ligation and transfected 293F fine. After transfection, 293F cells were stained with CFSE, and Hut-78 cells were stained with PKH26. Adhesion test was carried out in the presence of Mn2 +. 4. Gr4, Gr15 and Gr19, which were not infected with SIV / SHIV, were selected as the control group. According to the instructions of the kit, RNA was extracted from the tissues and real-time fluorescence quantitative RT-PCR was used to detect MAdCAM-1, ITGA4, ITGB7, NKX2.3, CCL25, CCR9, CCL28, CCR10, CCL19, CCL21, CCR7, RGS1, CCL22, CCR4, CCL20, CCR6, GPR183, FCGRT, PIGR, BCL-6, DDIT3, CCL21, CCL21, CCR7, CCR7, CCR7, R7, RGS1, CCL22, CCR4, CCL20, CCR6, GPR183, FCGRT, PIGR, BC Transcription levels of 23 genes, such as - alpha, IFN - gamma and so on. 5) According to Kangwei Century Tissue Protein Extraction Kit, four groups of animal tissue proteins were extracted, and the expression of MAdCAM-1 was detected by Western Blot, and the expression levels of CCL20, TNF-alpha, IFN-gamma, IL-17 and IL-6 were detected by ELISA.
Results: MAdCAM-1 plays an important role in mucosa-specific regression. Firstly, the MAdCAM-1 gene of rhesus monkey was cloned and its tissue distribution and changes after infection were studied. The hypothetical MAdCAM-1 protein of rhesus monkey, similar to human MAdCAM-1, contains a signal peptide, two N-terminal Ig-like domains, one mucin-like domain, one transmembrane domain and one cytoplasmic domain, but does not bind to the third Ig-like domain and IgA1-like domain in mice. The conserved region of LDT is in the first Ig like domain.
In normal rhesus monkey tissues, MAdCAM-1 mRNA was mainly expressed in gastrointestinal tract, spleen and lymph nodes, and was the highest in mesenteric lymph nodes. In intestine, the expression level of MAdCAM-1 mRNA was higher in large intestine than in small intestine, skin, thymus, oral mucosa and liver. The expression level of MAdCAM-1 mRNA in liver was the lowest. The expression level of MAdCAM-1 mRNA and MAdCAM-1 protein in intestinal mucosa decreased significantly.
To further understand the effect of SIV/SHIV infection on the expression of lymphatic homing-related genes, the expression of MAdACM-1 and its receptor alpha 4 beta-7 in intestinal mucosa of normal and infected animals was studied. The distribution of MAdCAM-1, ITGA4 and ITGB7 mRNA in normal intestinal mucosa was correlated, but the distribution of MAdCAM-1 and NKX2.3 was not correlated, but NKX2.3 was correlated with the distribution of MAdCAM-1 in intestine after infection, which may be involved in the regulation of MAdCAM-1 expression in intestine.
Further studies showed that SIV/SHIV infection also affected the levels of chemokines and receptors in gastrointestinal mucosa. After infection, intestinal chemokines CCL25, CCL28 and their receptors decreased in the small intestine, but increased in the large intestine, and the effects of different viral infections were different. The expression of chemokine CCL20 mRNA did not change significantly after infection, whereas the expression of chemokine CCR6 mRNA in duodenum and jejunum decreased significantly; the expression of chemokine CCL22 mRNA in jejunum decreased significantly after infection, and the expression of chemokine CCR4 mRNA in inguinal lymph nodes decreased significantly. Drop.
In addition, SIV/SHIV infection also affected the expression of cell migration regulator genes at transcriptional level: GPR183 regulated the migration of B cells in lymphoid follicles, decreased the expression of GPRI83 mRNA in spleen, mesenteric and inguinal lymph nodes, and decreased the expression of RGS1 mRNA in gastric fundus and duodenum.
In order to understand the relationship between the changes of regression-related molecules and other immunopathological changes in mucosa, we studied the changes of the transcription levels of inflammatory factors TNF-a and IFN-gamma after SIV/SHIV infection. Inflammatory factor TNF-alpha protein decreased significantly in jejunum and ileum, but decreased in small intestine and increased in large intestine as a whole; IFN-gamma protein did not change significantly, IL-6 protein increased significantly in ileum and cecum, and IL-17 protein increased significantly in rectum. It was found that FCGRT mRNA increased in intestinal mucosa, PIGR mRNA decreased in gastrointestinal tract and lymph nodes, BCL-6 mRNA decreased in small intestine and increased in large intestine after SIV/SHIV infection, while BCL-6 mRNA decreased in gastrointestinal mucosa (except rectum), spleen and lymph nodes after SHIV infection. The function of the disease may be affected.
CONCLUSIONS: In this study, the sequence of MAdCAM-1 cDNA in rhesus monkeys was obtained and found to be highly similar to that of human MAdCAM-1; 2) SIV/SHIV infection was found to affect the expression of MAdCAM-1 and receptor alpha 4 beta 7; 3) SIV/SHIV infection was found to affect the expression of multiple mucosal regression-related chemokines and receptors; 4) SIV/SHIV infection was found to affect the expression of multiple mucosal regression-related chemokines and receptors These results suggest that HIV-1 may affect mucosal and humoral immune function by influencing mucosal lymphocyte regression, and then influence mucosal cells and humoral immune function. It provides an important basis for understanding the pathological process of HIV/AIDS and finding new biological intervention targets.
【學(xué)位授予單位】：中國(guó)疾病預(yù)防控制中心
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R512.91
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本文編號(hào)：2179831
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