Davis B R, Schwartz D H, Marx J C, Johnson C E, Berry J M, Lyding J, Merigan T C, Zander A
Geraldine Brush Cancer Research Institute, Medical Research Institute, San Francisco, California.
J Virol. 1991 Apr;65(4):1985-90. doi: 10.1128/JVI.65.4.1985-1990.1991.
An important question in human immunodeficiency virus (HIV) pathogenesis is whether HIV-infected bone marrow CD34+ stem/progenitor cells serve as a significant reservoir of virus in HIV-infected individuals. Our data indicate that infection of bone marrow stem/progenitor cells with HIV occurs rarely, if ever, in vivo. In the present study, CD34+ cells were immunomagnetically purified from the bone marrow of HIV-seropositive individuals, and purified cells or colony-forming cells of the granulocyte/macrophage lineage were analyzed for HIV proviral DNA by the polymerase chain reaction. No HIV DNA was detected in colony-forming cells of the granulocyte/macrophage lineage from HIV-positive patients. Furthermore, no virus was found in CD34(+)-enriched cells from six of seven samples from asymptomatic HIV-infected individuals and four of four samples from patients with AIDS-related complex or AIDS. Thus, infected stem cells are not a major source of persistent HIV and do not account for hematopoietic suppression. These findings have positive implications for the concept of marrow reconstitution with autologous stem cells, genetically engineered for HIV resistance, following marrow-ablative antiviral therapy.
人类免疫缺陷病毒(HIV)发病机制中的一个重要问题是,在HIV感染个体中,被HIV感染的骨髓CD34 + 干细胞是否作为病毒的重要储存库。我们的数据表明,骨髓干细胞/祖细胞被HIV感染在体内极少发生,即便有也非常罕见。在本研究中,从HIV血清反应阳性个体的骨髓中免疫磁珠纯化CD34 + 细胞,并用聚合酶链反应分析纯化细胞或粒细胞/巨噬细胞系集落形成细胞中的HIV前病毒DNA。在HIV阳性患者的粒细胞/巨噬细胞系集落形成细胞中未检测到HIV DNA。此外,在无症状HIV感染个体的七个样本中的六个以及艾滋病相关综合征或艾滋病患者的四个样本中的四个的CD34(+)富集细胞中未发现病毒。因此,受感染的干细胞不是持续性HIV的主要来源,也不能解释造血抑制现象。这些发现对于在骨髓清除性抗病毒治疗后用经基因工程改造以抵抗HIV的自体干细胞进行骨髓重建的概念具有积极意义。