Circulating monocytes in HIV-1-infected viremic subjects exhibit an antiapoptosis gene signature and virus- and host-mediated apoptosis resistance.
Circulating monocytes in HIV-1-infected viremic subjects exhibit an antiapoptosis gene signature and virus- and host-mediated apoptosis resistance.
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DOI：
10.4049/jimmunol.0801450
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发表时间：
2009-04-01
期刊：
影响因子：
--
通讯作者：
Montaner LJ
中科院分区：
文献类型：
--
作者：
Giri MS;Nebozyhn M;Raymond A;Gekonge B;Hancock A;Creer S;Nicols C;Yousef M;Foulkes AS;Mounzer K;Shull J;Silvestri G;Kostman J;Collman RG;Showe L;Montaner LJ
当 CD4 T 细胞在 HIV-1 感染中减少时，可能允许循环单核细胞持续存在的机制尚未得到研究。我们对 HIV 感染者的循环单核细胞中的稳态基因表达特征进行了表征，并确定了由与 p53、CD40L、TNF 和 MAPK 信号网络相关的 38 个基因组成的稳定抗凋亡基因特征。我们证明了循环单核细胞中氯化镉或 Fas 配体诱导的细胞凋亡抗性，与来自同一感染受试者的 CD4 T 细胞的细胞凋亡增加相反，表明了该基因特征的重要性。作为体内的潜在机制，我们发现 HIV-1 病毒或激动剂趋化因子与单核细胞 CCR5 结合可作为独立的病毒和宿主调节剂，导致体外单核细胞凋亡抵抗力增加。我们还证明了体内 HIV-1 感染中循环单核细胞凋亡相关基因表达与体外病毒感染或单核细胞衍生巨噬细胞包膜暴露后可用数据集之间的一致性的证据。与单核细胞抗凋亡相关的体内基因表达的鉴定与艾滋病发病机制相关，因为它将有助于：1）维持单核细胞/巨噬细胞群中感染目标和HIV-1感染长期储存库的活力，2）尽管病毒持续高复制，但仍能保护对宿主生存至关重要的细胞亚群。
Mechanisms that may allow circulating monocytes to persist as CD4 T cells diminish in HIV-1 infection have not been investigated. We have characterized steady-state gene expression signatures in circulating monocytes from HIV-infected subjects and have identified a stable antiapoptosis gene signature comprised of 38 genes associated with p53, CD40L, TNF, and MAPK signaling networks. The significance of this gene signature is indicated by our demonstration of cadmium chloride- or Fas ligand-induced apoptosis resistance in circulating monocytes in contrast to increasing apoptosis in CD4 T cells from the same infected subjects. As potential mechanisms in vivo, we show that monocyte CCR5 binding by HIV-1 virus or agonist chemokines serves as independent viral and host modulators resulting in increased monocyte apoptosis resistance in vitro. We also show evidence for concordance between circulating monocyte apoptosis-related gene expression in HIV-1 infection in vivo and available datasets following viral infection or envelope exposure in monocyte-derived macrophages in vitro. The identification of in vivo gene expression associated with monocyte resistance to apoptosis is of relevance to AIDS pathogenesis since it would contribute to: 1) maintaining viability of infection targets and long-term reservoirs of HIV-1 infection in the monocyte/macrophage populations, and 2) protecting a cell subset critical to host survival despite sustained high viral replication.
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DOI：
10.1084/jem.187.5.711
发表时间：
1998-03-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Algeciras A;Dockrell DH;Lynch DH;Paya CV
通讯作者：
Paya CV
影响因子：
56.9
作者：
COCCHI, F;DEVICO, AL;LUSSO, P
通讯作者：
LUSSO, P
影响因子：
8
作者：
Gorospe, M;Cirielli, C;Holbrook, NJ
通讯作者：
Holbrook, NJ
影响因子：
3.8
作者：
Achanzar, WE;Achanzar, KB;Waalkes, MP
通讯作者：
Waalkes, MP
影响因子：
11.4
作者：
Asada, M;Yamada, T;Mizutani, S
通讯作者：
Mizutani, S