男男性行为HIV-1新近感染者中CRF01_AE毒株致病性及协同受体利用情况调查

发布时间：2018-05-14 11:50

  本文选题：I型人类免疫缺陷病毒 + 基因亚型　； 参考：《南通大学》2014年硕士论文

【摘要】：目的1.调查中国MSM HIV-1 CRF01_AE毒株新近感染人群的免疫状况及协同受体利用情况;2.探索MSM HIV-1 CRF01_AE毒株新近感染人群免疫状态与病毒亚型及协同受体利用的关系;3.探索新近感染CRF01_AE毒株的MSM人群体内X4病毒的来源。方法研究对象来自上海市疾病预防控制中心于2009年1月-2013年7月期间新诊断的MSM HIV-1阳性样本。从中选择年龄小于25岁的样本提取HIV-1 RNA,并进行pol及env区部分基因扩增。以流行病数据和分子进化数据(pol区混合碱基比例在0.44%以内)区分新近感染和慢性感染。使用协同受体在线预测软件WebPSSM和Geno2Pheno根据env区V3环的基因序列进行协同受体预测。不同亚型及CD4+T细胞分层的协同受体比例比较使用Fisher’s精确检验。CD4+T细胞计数与亚型及协同受体利用之间的关系用非参数检验Nemenyi法及Man-Whitney法进行检验。使用MrBayes3.1.2及BEAST软件构建进化树确认传播簇。结果1.364例MSM感染者中有276人被判定为新近感染,其中CRF01_AE感染者占63.8%(176/276),其次为CRF07_BC及B/B'亚型,分别占27.9%(77/276)及8.3%(23/276)。此外,8.69%(24/276)被鉴定为重组体。2.CRF01_AE、CRF07_BC及B亚型感染者的CD4+T细胞计数分别为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与CRF07_BC感染者之间CD4+T细胞计数的差异具有统计学意义(χ2=8.066,P=0.018),CRF01_AE与B亚型感染者之间CD4+T细胞计数的差异无统计学意义(χ2=1.774,P=0.412)。3.当分别使用algorithm I[Geno2pheno(FPR=10%)+webPSSM]和algorithm II[Geno2pheno(FPR=5%)+webPSSM]时,176例CRF01_AE感染者中利用CXCR4的比例分别为40.9%和32.4%,而两种方法均将所有的CRF07_BC和B亚型病毒预测为CCR5细胞噬性,不同亚型毒株之间协同受体利用的差异有统计学意义(χ2=55.348,P0.001;χ2=52.221,P0.001)。4.单独对176例CRF01_AE感染者分析发现,不同CD4+T细胞计数的感染者利用CXCR4的比例存在差异(algorithm I:χ2=12.228,P=0.006;algorithm II:χ2=11.940,P=0.008)。其中CD4+T细胞计数≤200 cells/μL的感染者利用CXCR4的比例最高,分别为76.2%(algorithm I)和61.9%(algorithm II)。5.对176例CRF01_AE感染者pol基因及env基因构建进化树发现,22例及16例X4病毒感染者参与簇的形成,X4病毒与R5病毒成簇的比例差异无统计学意义(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)。结论此次对年轻MSM HIV-1感染者的研究首次证实CRF01_AE毒株比CRF07_BC利用更高比例的CXCR4协同受体,这些高比例的X4病毒很可能是传播而来,这也许会导致较快的CD4+T细胞下降和加速疾病期的出现。因此,临床上需要对CRF01_AE感染者进行协同受体的预测以便早期治疗防止免疫系统功能的过早衰减而加速疾病进展。
[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，

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