Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0524, United States.
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0524, United States.
Virology. 2015 Sep;483:83-95. doi: 10.1016/j.virol.2015.04.004. Epub 2015 May 15.
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.
人巨细胞病毒（HCMV）潜伏在造血祖细胞和髓系未分化细胞中。髓系的成熟和分化会触发裂解复制。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 1,25-二羟维生素 D3 对 HCMV 复制的影响。有趣的是，1,25-二羟维生素 D3 诱导裂解复制，表现为 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 那样驱动感染性生命周期。确定 1,25-二羟维生素 D3 引发的信号通路将有助于更好地理解决定 HCMV 一旦感染髓系细胞后命运的潜在分子机制。
