本文選題：I型人類(lèi)免疫缺陷病毒 + 基因亞型��； 參考：《南通大學(xué)》2014年碩士論文

【摘要】：目的1.調(diào)查中國(guó)MSM HIV-1 CRF01_AE毒株新近感染人群的免疫狀況及協(xié)同受體利用情況;2.探索MSM HIV-1 CRF01_AE毒株新近感染人群免疫狀態(tài)與病毒亞型及協(xié)同受體利用的關(guān)系;3.探索新近感染CRF01_AE毒株的MSM人群體內(nèi)X4病毒的來(lái)源。方法研究對(duì)象來(lái)自上海市疾病預(yù)防控制中心于2009年1月-2013年7月期間新診斷的MSM HIV-1陽(yáng)性樣本。從中選擇年齡小于25歲的樣本提取HIV-1 RNA,并進(jìn)行pol及env區(qū)部分基因擴(kuò)增。以流行病數(shù)據(jù)和分子進(jìn)化數(shù)據(jù)(pol區(qū)混合堿基比例在0.44%以?xún)?nèi))區(qū)分新近感染和慢性感染。使用協(xié)同受體在線預(yù)測(cè)軟件WebPSSM和Geno2Pheno根據(jù)env區(qū)V3環(huán)的基因序列進(jìn)行協(xié)同受體預(yù)測(cè)。不同亞型及CD4+T細(xì)胞分層的協(xié)同受體比例比較使用Fisher’s精確檢驗(yàn)。CD4+T細(xì)胞計(jì)數(shù)與亞型及協(xié)同受體利用之間的關(guān)系用非參數(shù)檢驗(yàn)Nemenyi法及Man-Whitney法進(jìn)行檢驗(yàn)。使用MrBayes3.1.2及BEAST軟件構(gòu)建進(jìn)化樹(shù)確認(rèn)傳播簇。結(jié)果1.364例MSM感染者中有276人被判定為新近感染,其中CRF01_AE感染者占63.8%(176/276),其次為CRF07_BC及B/B'亞型,分別占27.9%(77/276)及8.3%(23/276)。此外,8.69%(24/276)被鑒定為重組體。2.CRF01_AE、CRF07_BC及B亞型感染者的CD4+T細(xì)胞計(jì)數(shù)分別為415.5(IQR:274.3-537.0)cells/μL、476.5(IQR:339.3-617.5)cells/μL及475.0(IQR:351.0-590.0)cells/μL。CRF01_AE與CRF07_BC感染者之間CD4+T細(xì)胞計(jì)數(shù)的差異具有統(tǒng)計(jì)學(xué)意義(χ2=8.066,P=0.018),CRF01_AE與B亞型感染者之間CD4+T細(xì)胞計(jì)數(shù)的差異無(wú)統(tǒng)計(jì)學(xué)意義(χ2=1.774,P=0.412)。3.當(dāng)分別使用algorithm I[Geno2pheno(FPR=10%)+webPSSM]和algorithm II[Geno2pheno(FPR=5%)+webPSSM]時(shí),176例CRF01_AE感染者中利用CXCR4的比例分別為40.9%和32.4%,而兩種方法均將所有的CRF07_BC和B亞型病毒預(yù)測(cè)為CCR5細(xì)胞噬性,不同亞型毒株之間協(xié)同受體利用的差異有統(tǒng)計(jì)學(xué)意義(χ2=55.348,P0.001;χ2=52.221,P0.001)。4.單獨(dú)對(duì)176例CRF01_AE感染者分析發(fā)現(xiàn),不同CD4+T細(xì)胞計(jì)數(shù)的感染者利用CXCR4的比例存在差異(algorithm I:χ2=12.228,P=0.006;algorithm II:χ2=11.940,P=0.008)。其中CD4+T細(xì)胞計(jì)數(shù)≤200 cells/μL的感染者利用CXCR4的比例最高,分別為76.2%(algorithm I)和61.9%(algorithm II)。5.對(duì)176例CRF01_AE感染者pol基因及env基因構(gòu)建進(jìn)化樹(shù)發(fā)現(xiàn),22例及16例X4病毒感染者參與簇的形成,X4病毒與R5病毒成簇的比例差異無(wú)統(tǒng)計(jì)學(xué)意義(pol:22/72=30.6%VS 36/104=34.6%,χ2=0.317,P0.05;env:16/72=22.2%VS 23/104=22.1%,χ20.001,P0.05)。結(jié)論此次對(duì)年輕MSM HIV-1感染者的研究首次證實(shí)CRF01_AE毒株比CRF07_BC利用更高比例的CXCR4協(xié)同受體,這些高比例的X4病毒很可能是傳播而來(lái),這也許會(huì)導(dǎo)致較快的CD4+T細(xì)胞下降和加速疾病期的出現(xiàn)。因此,臨床上需要對(duì)CRF01_AE感染者進(jìn)行協(xié)同受體的預(yù)測(cè)以便早期治療防止免疫系統(tǒng)功能的過(guò)早衰減而加速疾病進(jìn)展。
[Abstract]:Objective 1. To investigate the immune status and coreceptor utilization of the newly infected population of MSM HIV-1 CRF01_AE strain in China. Objective: to explore the relationship between immune status, virus subtype and coreceptor utilization in newly infected population of MSM HIV-1 CRF01_AE strain. To explore the source of X4 virus in MSM population newly infected with CRF01_AE strain. Methods MSM HIV-1 positive samples from Shanghai Centers for Disease Control and Prevention were newly diagnosed from January 2009 to July 2013. HIV-1 was extracted from samples younger than 25 years old, and pol and env regions were amplified. The proportion of mixed bases in pol region of epidemic data and molecular evolution data was less than 0.44%) to distinguish new infection from chronic infection. Coreceptor prediction software WebPSSM and Geno2Pheno were used to predict coreceptor according to the gene sequence of V3 loop in env region. Comparison of the proportion of coreceptors in different subtypes and CD4 T cell stratification. The relationship between the number of CD4 T cells, subtype and coreceptor utilization was examined by Fisher's accurate test. Nemenyi and Man-Whitney methods were used to test the relationship between the number of CD44T cells and the utilization of subtypes and coreceptors. MrBayes3.1.2 and BEAST software were used to construct the evolutionary tree to confirm the propagation cluster. Results among the 1.364 cases of MSM infection, 276 cases were classified as newly infected, of which CRF01_AE infection accounted for 63.8%, followed by CRF07_BC and B / B 'subtype (27.9% 77 / 276) and 8.3% 23 / 276% respectively. In addition, the CD4 T cell counts of patients with AECRF07BC and B subtype B were identified as recombinant. 2. The counts of CD4 T cells in patients with AECRF07BC and B subtype B were 415.5(IQR:274.3-537.0)cells/ 渭 L, 476.5g / 渭 L and 475.0(IQR:351.0-590.0)cells/ 渭 L.CRF01_AE, respectively. There was a statistically significant difference in the counts of CD4 T cells between 475.0(IQR:351.0-590.0)cells/ 渭 L.CRF01_AE and CRF07_BC infected persons (蠂 2 / 8.066 / P0. 018 P < 0. 018). There was a significant difference in CD4 T cell counts between 475.0(IQR:351.0-590.0)cells/ 渭 L.CRF01_AE and B subtype infected persons with CRF01AE and B subtype infection, respectively. There was no significant difference between the two groups (蠂 2, 1.774, P < 0. 412, P < 0. 3). When using algorithm I [Geno2phenoFPR10] webPSSM] and algorithm II [Geno2phenoFPR5 webPSSM], the proportion of using CXCR4 in 176 cases of CRF01_AE infection was 40.9% and 32.4%, respectively, while both methods predicted all CRF07_BC and B subtype viruses as CCR5 cell phagocytosis. There were significant differences in coreceptor utilization among different subtype strains (蠂 ~ 2 ~ 2 ~ (2) 55.348U P 0.001; 蠂 ~ (2 +) ~ (52.221) P _ (0.001) P ~ (0.001) 路4). The analysis of 176 cases of CRF01_AE infection alone found that there were differences in the proportion of using CXCR4 among patients with different CD4 T cell counts: 蠂 ~ 2 ~ 2 ~ 2 ~ (12.228) ~ P ~ (0.006) ~ 2: 蠂 ~ (2) ~ 2 ~ (11.940) P ~ (0.008). CD4 T cell count 鈮，

本文編號(hào)：1887735