Richardson-Burns Sarah M, Kleinschmidt-DeMasters B K, DeBiasi Roberta L, Tyler Kenneth L
Neuroscience Program, University of Colorado Health Sciences Center, Denver Veterans Affairs Medical Center, 80262, USA.
Arch Neurol. 2002 Dec;59(12):1930-6. doi: 10.1001/archneur.59.12.1930.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by JC virus (JCV) that occurs in immunocompromised patients. Demyelination of the CNS is a consequence of virus-induced killing of oligodendrocytes, although the exact mechanism of cell death is unknown.
To examine archival autopsy and surgical pathologic specimens from 8 patients with PML, including 6 patients with human immunodeficiency virus (HIV)-associated PML and 2 patients with non-HIV-associated PML, for evidence of apoptosis.
Apoptotic cells were identified by TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end in situ labeling) or immunohistochemical detection of activated caspase 3. The JCV-infected cells were identified by in situ hybridization for viral transcripts or immunohistochemical analysis for JCV T antigen.
Apoptosis of JCV-infected oligodendrocyte apoptosis was a prominent feature in all cases of both HIV- and non-HIV-associated PML. There were no differences between number or distribution of apoptotic cells identified by TUNEL or immunohistochemical analysis for activated caspase 3. Bizarre astrocytes were occasionally positive for JCV but were not apoptotic. Neurons, astrocytes, macrophages, and oligodendrocytes remote from lesions were neither apoptotic nor JCV infected.
Our study demonstrates that apoptosis occurs in oligodendrocytes associated with demyelinated lesions of patients with both HIV-associated and non-HIV-associated PML. There were no differences in degree, location, or type of infected or apoptotic cells between patients with HIV-associated and non-HIV-associated PML. The extent of apoptosis did not correlate with the presence or intensity of host inflammatory response. Accumulation of viral particles in nuclei of infected cells made it difficult to identify morphologic changes in the nucleus typically associated with apoptosis.
进行性多灶性白质脑病（PML）是一种由JC病毒（JCV）引起的中枢神经系统（CNS）脱髓鞘疾病，发生于免疫功能低下的患者。中枢神经系统脱髓鞘是病毒诱导少突胶质细胞死亡的结果，尽管细胞死亡的确切机制尚不清楚。
检查8例PML患者的存档尸检和手术病理标本，包括6例与人类免疫缺陷病毒（HIV）相关的PML患者和2例与非HIV相关的PML患者，以寻找凋亡证据。
通过TUNEL（末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端原位标记）或活化半胱天冬酶3的免疫组化检测来鉴定凋亡细胞。通过病毒转录本的原位杂交或JCV T抗原的免疫组化分析来鉴定JCV感染的细胞。
在所有HIV相关和非HIV相关的PML病例中，JCV感染的少突胶质细胞凋亡是一个突出特征。通过TUNEL或活化半胱天冬酶3的免疫组化分析鉴定的凋亡细胞数量或分布没有差异。奇异星形胶质细胞偶尔JCV呈阳性，但不发生凋亡。远离病变的神经元、星形胶质细胞、巨噬细胞和少突胶质细胞既不发生凋亡也未被JCV感染。
我们的研究表明，在与HIV相关和非HIV相关的PML患者脱髓鞘病变相关的少突胶质细胞中发生凋亡。HIV相关和非HIV相关的PML患者在感染或凋亡细胞的程度、位置或类型上没有差异。凋亡程度与宿主炎症反应的存在或强度无关。病毒颗粒在感染细胞核中的积累使得难以识别通常与凋亡相关的细胞核形态变化。
