Gibbons A E, Price P, Shellam G R
Department of Microbiology, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands.
Blood. 1995 Jul 15;86(2):473-81.
We have studied the effects of murine cytomegalovirus (MCMV) infection on bone marrow stem and progenitor cell populations to find an explanation for the defects in hematopoiesis that accompany CMV infections in patients. Sublethal MCMV infection of BALB/c mice resulted in a 5- to 10-fold decrease in the numbers of myeloid (colony-forming unit-granulocyte-macrophage [CFU-GM]) and erythroid (burst-forming unit-erythroid [BFU-E]) progenitor cells in the marrow, but not in primitive myeloerythroid progenitor cell (colony-forming unit-spleen [CFU-S]) numbers. In contrast, we observed a 10- to 20-fold reduction in CFU-S as well as CFU-GM and BFU-E in lethally infected mice. Depletion of marrow CFU-GM was less severe in C57BL/10 and C3H/HeJ mice, which are more resistant to the effects of MCMV infection. Treatment of bone marrow cells with MCMV preparations in vitro did not reduce the numbers of CFU-GM, although up to 10% of the cells were productively infected. This finding suggests that CFU-GM were not susceptible to lytic MCMV infection in vitro and are probably not eliminated by lytic infection in vivo. Increases in the frequencies of Sca-1+Lin- marrow cells, a population that includes cells with the characteristics of pluripotential stem cells, were observed in MCMV-infected BALB/c, C57BL/10, and DBA/2J mice. Increases in the frequencies of c-kit+Lin- marrow cells were only seen in DBA/2J mice. MCMV infection did not impair the function of pluripotential stem cells because transplantation of marrow from MCMV-infected donors into irradiated recipient mice resulted in successful reconstitution of the T, B, and myeloid cell lineages.
我们研究了鼠巨细胞病毒（MCMV）感染对骨髓干细胞和祖细胞群体的影响，以探寻患者CMV感染伴随造血功能缺陷的原因。对BALB/c小鼠进行亚致死剂量的MCMV感染，导致骨髓中髓系祖细胞（集落形成单位-粒细胞-巨噬细胞[CFU-GM]）和红系祖细胞（爆式红系集落形成单位[BFU-E]）数量减少5至10倍，但原始髓红系祖细胞（脾集落形成单位[CFU-S]）数量未减少。相比之下，我们观察到在致死感染的小鼠中，CFU-S以及CFU-GM和BFU-E减少了10至20倍。在对MCMV感染影响更具抗性的C57BL/10和C3H/HeJ小鼠中，骨髓CFU-GM的耗竭程度较轻。体外使用MCMV制剂处理骨髓细胞，虽然高达10%的细胞被有效感染，但CFU-GM的数量并未减少。这一发现表明，CFU-GM在体外不易受到MCMV裂解性感染，在体内可能也不会因裂解性感染而被清除。在MCMV感染的BALB/c、C57BL/10和DBA/2J小鼠中，观察到Sca-1+Lin-骨髓细胞频率增加，该群体包括具有多能干细胞特征的细胞。仅在DBA/2J小鼠中观察到c-kit+Lin-骨髓细胞频率增加。MCMV感染并未损害多能干细胞的功能，因为将来自MCMV感染供体的骨髓移植到受辐照的受体小鼠中，成功重建了T、B和髓系细胞谱系。
