The human cytomegalovirus lytic cycle is induced by 1,25-dihydroxyvitamin D3 in peripheral blood monocytes and in the THP-1 monocytic cell line.
The human cytomegalovirus lytic cycle is induced by 1,25-dihydroxyvitamin D3 in peripheral blood monocytes and in the THP-1 monocytic cell line.
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DOI：
10.1016/j.virol.2015.04.004
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发表时间：
2015-09
期刊：
影响因子：
3.7
通讯作者：
Miller WE
中科院分区：
文献类型：
--
作者：
Wu SE;Miller WE
人巨细胞病毒 (HCMV) 以潜伏形式存在于造血祖细胞和骨髓谱系内的未分化细胞中。沿骨髓谱系的成熟和分化触发裂解复制。在这里，我们使用外周血单核细胞和单核细胞系 THP-1 来研究 1,25-二羟基维生素 D3 对 HCMV 复制的影响。有趣的是，1,25-二羟基维生素 D3 会诱导裂解性复制，其特点是 HCMV 基因表达上调和感染性病毒的产生。此外，我们证明 1,25-二羟基维生素 D3 的作用与单核细胞的成熟/分化相关，而不是直接刺激 MIEP。这些结果有些令人惊讶，因为 1,25-二羟基维生素 D3 通常会增强对细菌和病毒的免疫力，而不是像 HCMV 那样驱动感染生命周期。定义 1,25-二羟基维生素 D3 引发的信号通路将有助于更好地理解决定 HCMV 一旦感染骨髓系细胞后命运的分子机制。
Human cytomegalovirus (HCMV) resides in a latent form in hematopoietic progenitors and undifferentiated cells within the myeloid lineage. Maturation and differentiation along the myeloid lineage triggers lytic replication. Here, we used peripheral blood monocytes and the monocytic cell line THP-1 to investigate the effects of 1,25-dihydroxyvitamin D3 on HCMV replication. Interestingly, 1,25-dihydroxyvitamin D3 induces lytic replication marked by upregulation of HCMV gene expression and production of infectious virus. Moreover, we demonstrate that the effects of 1,25-dihydroxyvitamin D3 correlate with maturation/differentiation of the monocytes and not by directly stimulating the MIEP. These results are somewhat surprising as 1,25-dihydroxyvitamin D3 typically boosts immunity to bacteria and viruses rather than driving the infectious life cycle as it does for HCMV. Defining the signaling pathways kindled by 1,25-dihydroxyvitamin D3 will lead to a better understanding of the underlying molecular mechanisms that determine the fate of HCMV once it infects cells in the myeloid lineage.