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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Differential HIV-1 replication in neonatal and adult blood mononuclear cells is influenced at the level of HIV-1 gene expression
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Differential HIV-1 replication in neonatal and adult blood mononuclear cells is influenced at the level of HIV-1 gene expression

机译：新生儿和成人血液单核细胞中HIV-1的差异复制受HIV-1基因表达水平的影响

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The majority of HIV-1-infected neonates and infants have a higher level of viremia and develop AIDS more rapidly than infected adults, including differences seen in clinical manifestations. To determine the mechanisms of HIV-1 infection in neonates vs. adults, we compared the replication kinetics of HIV-1 in neonatal (cord) and adult blood T lymphocytes and monocyte-derived macrophages (MDM) from seven different donors. We found that HIV-1 replicated 3-fold better in cord blood T lymphocytes compared with adult blood T lymphocytes and 9-fold better in cord MDM than adult MDM. We also show that this differential HIV-1 replication did not depend on differences in cell proliferative capabilities, cell surface expression of CD4, CXCR4, and CCR5, or in the amount of PCR products of reverse transcription, DNA synthesis, and translocation of preintegration complex into the nucleus in cord and adult T lymphocytes and MDM. Furthermore, using a single-cycle replication competent HIV-1-NL4-3-Env(-) luciferase amphotropic virus, which measures HIV-1 transcriptional activity independent of receptor and coreceptor expression, we found there was a 3-fold increase of HIV-1 LTR-driven luciferase expression in cord T lymphocytes compared with adult T lymphocytes and 10-fold in cord MDM than in adult MDM. The HIV-1 LTR-driven luciferase expression correlated with HIV-1 LTR transcription, as measured by ribonuclease protection assay. These data suggest that the increased replication of HIV-1 in cord blood compared with adult blood mononuclear cells is regulated at the level of HIV-1 gene expression, resulting in a higher level of viremia and faster disease progression in neonates than adults.
机译：大多数受HIV-1感染的新生儿和婴儿比受感染的成年人具有更高的病毒血症水平和更快速的发展AIDS，包括临床表现上的差异。为了确定新生儿与成人之间HIV-1感染的机制，我们比较了来自七个不同捐赠者的新生儿（脐带血）和成人血液T淋巴细胞和单核细胞衍生巨噬细胞（MDM）中HIV-1的复制动力学。我们发现，与成年血液T淋巴细胞相比，HIV-1在脐血T淋巴细胞中复制的能力要比成年MDM好3倍，在脐带MDM中的复制能力要好9倍。我们还表明，这种差异化的HIV-1复制并不取决于细胞增殖能力，CD4，CXCR4和CCR5的细胞表面表达或逆转录，DNA合成和整合前复合体易位的PCR产物量的差异。进入脐带，成年T淋巴细胞和MDM的细胞核。此外，使用能够独立于受体和共受体表达而测量HIV-1转录活性的单周期复制型HIV-1-NL4-3-Env（-）荧光素酶两性病毒，我们发现HIV含量增加了3倍与成人T淋巴细胞相比，脐带T淋巴细胞中-1 LTR驱动的荧光素酶表达高，而成人MDM中脐带MDM中的-1倍。 HIV-1 LTR驱动的萤光素酶表达与HIV-1 LTR转录相关，如通过核糖核酸酶保护试验测定的。这些数据表明，与成人血液单核细胞相比，脐带血中HIV-1的复制增加受到HIV-1基因表达水平的调节，导致新生儿的病毒血症水平更高，疾病进展更快。

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