Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells
Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells
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DOI：
10.1073/pnas.95.7.3937
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发表时间：
1998-03-31
影响因子：
11.1
通讯作者：
Mocarski, ES
中科院分区：
文献类型：
--
作者：
Hahn, G;Jores, R;Mocarski, ES
造血细胞及其祖细胞在人巨细胞病毒潜伏期和再活化中起重要作用，已经在共表达CD 33和CD 15或CD 33和CD 14沿着树突状细胞标志物CD 1a和CD 10的髓系定向祖细胞的限定群体中评价了潜伏感染，发现这些CD 33（+）细胞群支持病毒潜伏期和表达。相关的转录物并在人成纤维细胞存在下分化时经历生产性病毒复制的再活化，当骨髓细胞在成纤维细胞条件培养基或补充某些细胞因子的培养基中进行时，也观察到再活化（干扰素γ、肿瘤坏死因子α、白细胞介素4或粒细胞-巨噬细胞集落刺激因子），表明细胞分化途径是再活化的决定因素，还发现更原始的CD 34（+）造血细胞对病毒感染敏感，并且当这些细胞分化成CD 33（+）谱系定型群体时，潜伏期得以维持。发现从自然感染个体分离的0.01%至0.001%的CD 33（+）CD 14（+）或CD 33（+）CD 15（+）骨髓单个核细胞表达潜伏转录本。因此，巨细胞病毒在健康血清阳性宿主中的小百分比的骨髓和树突状细胞祖细胞内携带。病毒再活化可由与炎症反应相关的因素触发。
Hematopoietic cells and their progenitors play important roles in human cytomegalovirus latency and reactivation, Latent infection has been evaluated in defined populations of myeloid-lineage-committed progenitor cells coexpressing CD33 and CD15 or CD33 and CD14 along with the dendritic cell markers CD1a and CD10, These CD33(+) cell populations were found to support latency and expression of viral latency-associated transcripts and to undergo reactivation of productive viral replication when differentiated in the presence of human fibroblasts, Reactivation was also observed when myeloid cells were carried in the presence of fibroblast conditioned medium or medium supplemented with certain cytokines (interferon gamma, tumor necrosis factor alpha, interleukin 4, or granulocyte-macrophage colony-simulating factor), suggesting that cell differentiation pathways act as determinants of reactivation, More primitive CD34(+) hematopoietic cells were also found to be susceptible to viral infection and latency was maintained as these cells differentiated into CD33(+)-lineage-committed populations. Between 0.01% and 0.001% of CD33(+) CD14(+) or CD33(+) CD15(+) bone marrow mononuclear cells isolated from naturally infected individuals were found to express latent transcripts. Thus, cytomegalovirus is carried within a small percentage of myeloid and dendritic cell progenitors in the healthy seropositive host, Virus reactivation may be triggered by factors associated with the inflammatory response.