Wei G, Liu C K, Atwood W J
Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island, RI 02912, USA.
J Neurovirol. 2000 Apr;6(2):127-36. doi: 10.3109/13550280009013156.
The human polyomavirus, JCV, is the etiological agent of the fatal central nervous system demyelinating disease, progressive multifocal leukoencephalopathy (PML). In PML patients, JC Virus (JCV) can be detected in glial cells in the central nervous system (CNS); in B-lymphocytes in the peripheral blood, bone marrow, spleen, and tonsil; and in tonsillar stromal cells. In vitro, JCV infects glial cells, tonsillar stromal cells, and to a limited extent B-lymphocytes. The presence or absence of as yet unidentified cell type specific transcription factors contributes to the restricted tropism of JCV for these cell types. However, several studies indicate that cell surface receptors may also contribute to the limited host range of JCV. To examine this latter possibility we measured the binding of purified JCV virions to primary cultures of glial cells, tonsillar stromal cells, peripheral blood lymphocytes, and to several established cell lines. Our results demonstrate that JCV binds to primary glial cells, stromal cells, and B cells, but does not bind to primary T cells. In contrast, JCV bound to all cell lines tested, including the Namalwa B cell line and the Jurkat T cell line. These data are novel and demonstrate that JCV selectively interacts with cells in vivo that are known to be susceptible to infection. This selectivity appears to be lost when one examines virus binding to a variety of human, monkey, or mouse tumor cell lines. We next examined the susceptibility of primary peripheral blood lymphocytes and the Namalwa B cell line to infection with JCV. Our results demonstrate that the majority of infectious JCV virions remain cell surface associated and do not efficiently establish infection of B cells. This may explain the in vivo observation that JCV DNA is frequently detected in association with lymphocytes by PCR but that JCV mRNA is rarely detected in association with lymphocytes by reverse transcriptase PCR. These results also confirm previous data regarding the association of JCV with human B cells in vivo and support the hypothesis that B cells may be involved in trafficking of JCV to the CNS.
人多瘤病毒JCV是致命的中枢神经系统脱髓鞘疾病——进行性多灶性白质脑病（PML）的病原体。在PML患者中，可在中枢神经系统（CNS）的神经胶质细胞、外周血、骨髓、脾脏和扁桃体中的B淋巴细胞以及扁桃体基质细胞中检测到JC病毒（JCV）。在体外，JCV可感染神经胶质细胞、扁桃体基质细胞，并在一定程度上感染B淋巴细胞。目前尚未确定的细胞类型特异性转录因子的存在与否导致了JCV对这些细胞类型的嗜性受限。然而，多项研究表明，细胞表面受体也可能导致JCV的宿主范围有限。为了研究后一种可能性，我们测量了纯化的JCV病毒粒子与神经胶质细胞、扁桃体基质细胞、外周血淋巴细胞的原代培养物以及几种已建立的细胞系的结合情况。我们的结果表明，JCV可与原代神经胶质细胞、基质细胞和B细胞结合，但不与原代T细胞结合。相比之下，JCV可与所有测试的细胞系结合，包括Namalwa B细胞系和Jurkat T细胞系。这些数据是新颖的，表明JCV在体内与已知易受感染的细胞选择性相互作用。当研究病毒与多种人、猴或小鼠肿瘤细胞系的结合时，这种选择性似乎丧失了。接下来，我们检测了原代外周血淋巴细胞和Namalwa B细胞系对JCV感染的敏感性。我们的结果表明，大多数具有感染性的JCV病毒粒子仍与细胞表面结合，不能有效地建立对B细胞的感染。这可能解释了在体内观察到的现象，即通过PCR经常在淋巴细胞中检测到JCV DNA，但通过逆转录酶PCR很少在淋巴细胞中检测到JCV mRNA。这些结果也证实了先前关于JCV在体内与人B细胞关联的数据，并支持B细胞可能参与JCV向CNS转运的假说。
