Human cytomegalovirus persists in myeloid progenitors and is passed to the myeloid progeny in a latent form

Human cytomegalovirus persists in myeloid progenitors and is passed to the myeloid progeny in a latent form
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DOI:
10.1111/j.1365-2141.2004.05056.x
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发表时间:
2004-08-01
影响因子:
6.5
通讯作者:
St Jeor, S
St Jeor, S
中科院分区:
医学2区
文献类型:
--
作者:
Khaiboullina, SF;Maciejewski, JP;St Jeor, S

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CD 34(+)祖细胞可携带潜伏的人巨细胞病毒(HCMV),但HCMV潜伏的机制尚不清楚。我们研究了造血谱系限制对潜伏HCMV建立和传播到子代细胞的影响。在体外感染和潜伏感染的造血祖细胞来源于HCMV血清阳性供体进行了研究。应用单克隆聚合酶链反应和荧光原位杂交技术检测骨髓前体细胞(BMP)中HCMV DNA的存在。发现CMV DNA的存在仅限于髓系祖细胞,并且自然感染的细胞中HCMV感染细胞的百分比低于体外感染的细胞。红系分化导致流产感染,病毒核酸在红细胞前体中持续存在。在来自HCMV血清阴性供体的BMP细胞中,HCMV DNA定位于细胞核中。骨髓祖细胞在粒细胞-巨噬细胞集落刺激因子(GMCSF)的存在下维持HCMV DNA延长的时间。在整个培养过程中未检测到病毒产生,但培养前后潜伏感染细胞数量的比较表明,造血祖细胞的增殖可能导致潜伏感染细胞的扩增。
CD34(+) progenitor cells can harbour latent human cytomegalovirus (HCMV); however, the mechanisms of HCMV latency remain unclear. We have investigated the effects of the haematopoietic lineage restriction on the establishment and spread of the latent HCMV to progeny cells. In vitro-infected and latently-infected haematopoietic progenitor cells derived from HCMV seropositive donors were studied. The presence of HCMV DNA in bone marrow progenitor (BMP) cells was determined by single colony polymerase chain reaction and fluorescent in situ hybridization (FISH). The presence of CMV DNA was found to be restricted to myeloid progenitors and the percentage of HCMV-infected cells was lower in naturally-infected cells than in in vitro-infected cells. Erythroid differentiation resulted in an abortive infection with persistence of the viral nucleic acids in red cell precursors. In BMP cells from HCMV seronegative donors, HCMV DNA was localized in the nucleus. Bone marrow progenitors in the presence of granulocyte-macrophage colony stimulating factor (GMCSF) maintained HCMV DNA for extended periods of time. No viral production could be detected throughout the culture but the comparison of the numbers of latently-infected cells prior to and after the culture suggests that proliferation of haematopoietic progenitor cells may lead to the expansion of latently-infected cells.