Maciejewski J P, Bruening E E, Donahue R E, Mocarski E S, Young N S, St Jeor S C
National Heart, Lung and Blood Institute, Cell Biology Section, National Institutes of Health, Bethesda, MD.
Blood. 1992 Jul 1;80(1):170-8.
The susceptibility of hematopoietic progenitor cells to infection by human cytomegalovirus (HCMV) was investigated using several strains of HCMV, including the recombinant strain RC256. RC256 is derived from the laboratory strain Towne and contains the Escherichia coli LacZ gene coding for beta-galactosidase (beta-gal) regulated by an early HCMV promoter. Expression of LacZ allowed the detection of HCMV in individual hematopoietic cells. Clonogeneic bone marrow (BM) progenitors, including CD34+ cells, could be infected with HCMV and would then form normal hematopoietic colonies. By polymerase chain reaction (PCR) amplification of DNA, HCMV could be detected in both erythroid and myeloid colonies. LacZ activity was observed predominantly in cells of myelomonocytic lineage. When cells derived from HCMV-infected progenitors were cocultivated with permissive human fibroblasts, infectious virus expressing LacZ was recovered. Although no characteristic HCMV cytopathology was observed in BM colonies, high virus to cell ratios resulted in a moderate inhibition of colony formation. Since infected hematopoietic progenitors can harbor HCMV for weeks and through several differentiation steps in culture, we postulate that in vivo these cells may serve as a reservoir of latent virus and contribute to HCMV dissemination.
利用包括重组毒株RC256在内的几种人巨细胞病毒(HCMV)毒株,研究了造血祖细胞对HCMV感染的易感性。RC256源自实验室毒株Towne,含有由HCMV早期启动子调控的编码β-半乳糖苷酶(β-gal)的大肠杆菌LacZ基因。LacZ的表达使得能够在单个造血细胞中检测到HCMV。包括CD34+细胞在内的克隆源性骨髓(BM)祖细胞能够被HCMV感染,随后形成正常的造血集落。通过DNA的聚合酶链反应(PCR)扩增,在红系和髓系集落中均能检测到HCMV。LacZ活性主要在髓单核细胞系的细胞中观察到。当将源自HCMV感染祖细胞的细胞与允许性人成纤维细胞共培养时,可回收表达LacZ的感染性病毒。尽管在BM集落中未观察到特征性的HCMV细胞病变,但高病毒与细胞比例导致集落形成受到中度抑制。由于受感染的造血祖细胞能够在培养中携带HCMV数周并经历几个分化步骤,我们推测在体内这些细胞可能作为潜伏病毒的储存库,并有助于HCMV的传播。