MicroRNA-29 family expression and its relation to antiviral immune response and viro-immunological markers in HIV-1-infected patients.

MicroRNA-29 family expression and its relation to antiviral immune response and viro-immunological markers in HIV-1-infected patients.
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DOI:
10.1186/s12879-015-0768-4
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发表时间:
2015-02-12
影响因子:
3.7
通讯作者:
Scagnolari C
Scagnolari C
中科院分区:
医学3区
文献类型:
--
作者:
Monteleone K;Selvaggi C;Cacciotti G;Falasca F;Mezzaroma I;D'Ettorre G;Turriziani O;Vullo V;Antonelli G;Scagnolari C

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一些体外研究表明,microRNA-29(miRNA-29)家族参与调节HIV-1和IL-32的表达,IL-32是一种抗HIV-1细胞因子。为了研究miRNA-29家族在体内感染HIV-1中的作用,我们用RT-Taqman方法比较了58例HIV-1感染者、单纯抗逆转录病毒治疗患者和21名性别和年龄匹配的HIV-1血清阴性健康献血者PBMC中miRNA-29的表达。并评价miRNA-29水平与HIV-1病毒免疫标志物及抗病毒免疫应答激活率的关系。此外,我们还分析了5例经抗逆转录病毒治疗的HIV-1感染者的CD4+T淋巴细胞和CD14+单核细胞中miRNA-29的表达。HIV-1感染者的miRNA-29b水平高于对照组(p < 0.001)。与HIV-1RNA水平和T淋巴细胞计数均无相关性,而miRNA-29-a/c水平与整合的HIV-1DNA显著相关(miRNA-29a:p = 0.009,r = −0.448;miRNA-29c:p = 0.029;r = −0.381)。当HIV-1感染患者根据他们的血浆HIV-1RNA和CD4+T细胞计数进行分组时,我们还发现,miRNA-29c表达水平最低的患者表现为高病毒血症、低CD4+T细胞计数和高水平的整合HIV-1 DNA。此外,miRNA-29b水平与IL-32nonα水平呈正相关(p = 0.028;r = −0.298)。表达高水平miRNA-29b的患者显示低水平的MxA,这是一种干扰素刺激基因,也是由IL-32诱导的(p = 0.006 r = −0.397)。最后,我们发现CD4+T淋巴细胞和CD14+单核细胞具有相似的miRNA-29a/b/c表达模式,但在这两个细胞亚群中miRNA-29a/b/c、IL-32亚型和mxa的含量存在很大差异。MiRNA-29家族可影响HIV-1感染的临床进展、HIV-1前病毒载量和针对HIV-1的先天免疫反应。
Several in vitro studies suggested the microRNA-29 (miRNA-29) family is involved in regulating HIV-1 and modulating the expression of interleukin (IL)-32, an anti-HIV-1 cytokine. To investigate the contribution of the miRNA-29 family to HIV-1 infection in vivo, we compared miRNA-29 expression in PBMC collected from 58 HIV-1-infected patients, naïve for antiretroviral therapy, and 21 gender- and age-matched HIV-1 seronegative healthy donors, using RT-Taqman assays. The relation between miRNA-29 levels and HIV-1 viro-immunological markers and the activation rate of antiviral immune response were also evaluated. In addition, we profiled miRNA-29 expression in CD4+ T lymphocytes and CD14+ monocytes collected from 5 antiretroviral treated HIV-1 infected patients. miRNA-29b levels were higher in HIV-1-infected patients than in the control group (p < 0.001). There were no correlations with either HIV-1 RNA levels or CD4+ T count, whereas a significant correlation was found between miRNA-29-a/c levels and integrated HIV-1 DNA (miRNA-29a: p = 0.009, r = −0.448; miRNA-29c: p = 0.029; r = −0.381). When the HIV-1-infected patients were grouped on the basis of their plasma HIV-1 RNA and CD4+ T cell count, we also found that patients expressing the lowest levels of miRNA-29c showed high viraemia, low CD4+ T cell count and high levels of integrated HIV-1 DNA. Moreover, miRNA-29b levels were correlated with those of IL-32nonα (p = 0.028; r = −0.298). Patients expressing higher levels of miRNA-29b showed lower levels of MxA, an interferon-stimulated gene, also induced by IL-32 (p = 0.006 r = −0.397). Lastly, we found that CD4+ T lymphocytes and CD14+ monocytes shared similar miRNA-29a/b/c expression patterns but the amount of miRNA-29a/b/c, IL-32 isoforms and MxA were highly variable in these two cellular subsets. The miRNA-29 family could influence the clinical progression of HIV-1 infection, the HIV-1 proviral load and the innate immune response against HIV-1.
IL-32-PAR2轴是一种先天免疫传感器,为LPS-TRIF轴提供了替代信号。
DOI: 10.1038/srep02960
发表时间: 2013-10-16
期刊: SCIENTIFIC REPORTS
影响因子: 4.6
作者:
Nakayama, Masanori;Niki, Yasuo;Kawasaki, Toshiki;Takeda, Yuki;Ikegami, Hiroyasu;Toyama, Yoshiaki;Miyamoto, Takeshi
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