JC virus infection of hematopoietic progenitor cells, primary B lymphocytes, and tonsillar stromal cells: Implications for viral latency

JC virus infection of hematopoietic progenitor cells, primary B lymphocytes, and tonsillar stromal cells: Implications for viral latency
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DOI:
10.1128/jvi.70.10.7004-7012.1996
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发表时间:
1996-10-01
影响因子:
5.4
通讯作者:
Major, EO
Major, EO
中科院分区:
医学2区
文献类型:
--
作者:
Monaco, MCG;Atwood, WJ;Major, EO

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人类多瘤病毒JC病毒(JCV)感染中枢神经系统中的髓鞘生成细胞,导致致命的脱髓鞘疾病进行性多灶性白质脑病(PML)。JCV诱导的PML最常发生在免疫抑制个体中,在人类免疫缺陷I型感染患者中发病率最高,占所有AIDS病例的4%至6%。尽管JCV靶向中枢神经系统中的高度特化细胞,但感染广泛,全世界超过80%的人群显示血清抗体。许多临床和实验室研究现已将PML的发病机制与淋巴细胞中的JCV感染联系起来。例如,JCV感染的淋巴细胞被认为是淋巴组织中潜伏感染再激活后病毒进入大脑的可能载体。为了进一步确定与JCV相关的细胞嗜性,我们尝试感染免疫系统细胞,包括来源于人胎肝的CD 34(+)造血祖细胞、原代人B淋巴细胞和人扁桃体基质细胞。我们的结果表明,这些细胞类型以及CD 34(+)人细胞系KG-1a对JCV感染敏感,然而,JCV不能,感染KG-1,一种CD 34(+)细胞系,当用佛波醇酯处理时,其分化成巨噬细胞样细胞。此外,通过流式细胞术从PML患者分离外周血B淋巴细胞证实了JCV感染。这些结果提供了直接证据,JCV不是严格嗜神经的,但可以感染CD 34(+)造血祖细胞和那些分化成淋巴细胞而不是单核细胞谱系的细胞。
The human polyomavirus JC virus (JCV) infects myelin-producing cells in the central nervous system, resulting in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV-induced PML occurs most frequently in immunosuppressed individuals, with the highest incidence in human immunodeficiency type I-infected patients, ranging between 4 and 6% of all AIDS cases, Although JCV targets a highly specialized cell in the central nervous system, infection is widespread, dth more than 80% of the human population worldwide demonstrating serum antibodies. A number of clinical and laboratory studies have now linked the pathogenesis of PML with JCV infection in lymphoid cells. For example, JCV-infected lymphocytes have been suggested as possible carriers of virus to the brain following reactivation of a latent infection in lymphoid tissues. To further define the cellular tropism associated with JCV, we have attempted to infect immune system cells, including CD34(+) hematopoietic progenitor cells derived from human fetal liver, primary human B lymphocytes, and human tonsillar stromal cells, Our results demonstrate that these cell types as well as a CD34(+) human cell line, KG-1a, are susceptible to JCV infection, JCV cannot, however, infect KG-1, a CD34(+) cell line which differentiates into a macrophage-like cell when treated with phorbol esters, In addition, peripheral blood B lymphocytes isolated by how cytometry from a PML patient demonstrate JCV infection. These results provide direct evidence that JCV is not strictly neurotropic hut can infect CD34(+) hematopoietic progenitor cells and those cells which have differentiated into a lymphocytic, but not monocytic, lineage.