Watanabe M, Ringler D J, Nakamura M, DeLong P A, Letvin N L
Harvard Medical School, New England Regional Primate Research Center, Southborough, Massachusetts 01772.
J Virol. 1990 Feb;64(2):656-63. doi: 10.1128/JVI.64.2.656-663.1990.
The pathogenic mechanisms underlying the depressed hematopoietic functions seen in human immunodeficiency virus-infected individuals were explored in rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIVmac). Bone marrow hematopoietic progenitor cell colony formation, both granulocyte/macrophage (CFU-GM) and erythrocyte (BFU-E), was shown to be decreased in number in SIVmac-infected rhesus monkeys. SIVmac was readily isolated from bone marrow cells of infected monkeys and was shown to be harbored in macrophages rather than T lymphocytes. The in vitro infection of normal bone marrow cells by SIVmac inhibited colony formation. A striking in vivo correlation between increased SIVmac load in bone marrow cells and decreased hematopoietic progenitor cell colony growth was also shown. Finally, inhibition of SIVmac replication in bone marrow macrophages resulted in increased progenitor cell colony growth from bone marrow cells. These results suggest that the infection of bone marrow macrophages by the acquired immunodeficiency syndrome (AIDS) virus may contribute to depressed bone marrow hematopoietic progenitor cell growth. Moreover, inhibition of AIDS virus replication in these macrophages might induce significant improvement in hematopoietic function.
在感染猕猴猿猴免疫缺陷病毒（SIVmac）的恒河猴中，研究了人类免疫缺陷病毒感染个体中所见造血功能低下的致病机制。在感染SIVmac的恒河猴中，骨髓造血祖细胞集落形成，即粒细胞/巨噬细胞集落（CFU-GM）和红细胞集落（BFU-E）的数量均减少。SIVmac很容易从受感染猴子的骨髓细胞中分离出来，并且显示存在于巨噬细胞而非T淋巴细胞中。SIVmac对正常骨髓细胞的体外感染抑制了集落形成。还显示骨髓细胞中SIVmac载量增加与造血祖细胞集落生长减少之间存在显著的体内相关性。最后，抑制骨髓巨噬细胞中SIVmac的复制导致骨髓细胞中祖细胞集落生长增加。这些结果表明，获得性免疫缺陷综合征（AIDS）病毒对骨髓巨噬细胞的感染可能导致骨髓造血祖细胞生长受到抑制。此外，抑制这些巨噬细胞中AIDS病毒的复制可能会显著改善造血功能。
