In vitro suppression of normal human bone marrow progenitor cells by human immunodeficiency virus.

In vitro suppression of normal human bone marrow progenitor cells by human immunodeficiency virus.
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人类免疫缺陷病毒对正常人骨髓祖细胞的体外抑制。

DOI:
10.1128/jvi.65.4.1765-1769.1991
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发表时间:
1991
影响因子:
5.4
通讯作者:
Chatis,PA
Chatis,PA
中科院分区:
医学2区
文献类型:
--
作者:
Steinberg,HN;Crumpacker,CS;Chatis,PA

文献摘要

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以感染复数(MOI)范围为0.0001:1至1:1逆转录酶(RT)单位孵育正常人非贴壁和T细胞耗竭的骨髓细胞,导致祖细胞的红系爆发形成单位(BFU-E)、粒细胞-巨噬细胞(CFU-GM)和T淋巴细胞(CFU-TL)集落的体外生长受到剂量依赖性抑制。在病毒与骨髓细胞比例为1:1时观察到对集落形成的最大抑制。在该MOI下,BFU-E和CFU-GM集落被抑制60 - 80%,而CFU-TL集落被完全抑制。在0.1:1的MOI下也观察到菌落形成的抑制,但在病毒的进一步对数稀释下没有观察到。将病毒与gp 160抗体一起孵育导致干细胞抑制的完全逆转和体外集落生长的正常化。对于BFU-E和CFU-GM集落,在抗体稀释度高达1:100时观察到这种逆转,在滴度大于1:500时不再观察到这种逆转。CFU-TL集落数在1:10和1:50之间的滴度下标准化。人类免疫缺陷病毒(HIV)也抑制了50%的CD 34+干细胞部分衍生的集落的生长。感染的CD 34+细胞和T-细胞耗尽,非粘附细胞馏分证明了通过检测与HIV特异性DNA探针扩增后,通过聚合酶链反应。结果表明,HIV可以直接感染人骨髓祖细胞,影响其体外增殖和产生集落的能力。结果表明,该病毒在骨髓抑制中的直接作用和在艾滋病患者中观察到的血细胞减少的可能机制。
Incubation of normal human nonadherent and T-cell-depleted bone marrow cells with HIVIIIB at multiplicities of infection (MOI) ranging from 0.0001:1 to 1:1 reverse transcriptase (RT) units resulted in the dose-dependent suppression of the in vitro growth of erythroid burst-forming unit (BFU-E), granulocyte-macrophage (CFU-GM), and T-lymphocyte (CFU-TL) colonies of progenitor cells. Maximum inhibition of colony formation was observed at a 1:1 ratio of virus to bone marrow cells. At this MOI, BFU-E and CFU-GM colonies were inhibited by 60 to 80%, while CFU-TL colonies were totally suppressed. Inhibition of colony formation was also observed at an MOI of 0.1:1 but not with further log dilutions of the virus. Incubation of the virus with antibody to gp160 resulted in the complete reversal of stem cell suppression and the normalization of colony growth in vitro. For BFU-E and CFU-GM colonies, this reversal was observed with dilutions of antibody up to 1:100 and was no longer observed at titers greater than 1:500. The CFU-TL colony number normalized at titers between 1:10 and 1:50. Human immunodeficiency virus (HIV) also suppressed by 50% the growth of colonies derived from CD34+ stem cell fractions. Infection of CD34+ cells and T-cell-depleted, nonadherent cell fractions was demonstrated by detection with HIV-specific DNA probe following amplification by polymerase chain reaction. The results suggest that HIV can directly infect human bone marrow progenitor cells and affect their ability to proliferate and give rise to colonies in vitro. The results indicate a direct role for the virus in bone marrow suppression and a possible mechanism for the cytopenias observed in patients with AIDS.