Murine cytomegalovirus induces apoptosis in non-infected cells of the developing mouse brain and blocks apoptosis in primary neuronal culture
Murine cytomegalovirus induces apoptosis in non-infected cells of the developing mouse brain and blocks apoptosis in primary neuronal culture
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DOI：
10.1007/s004010050890
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发表时间：
1998-09-01
影响因子：
12.7
通讯作者：
Tsutsui, Y
中科院分区：
文献类型：
--
作者：
Kosugi, I;Shinmura, Y;Tsutsui, Y
巨细胞病毒（CMV）是先天性感染的最常见原因，导致出生缺陷，如小头畸形。在这项研究中，我们发现，细胞凋亡是诱导小鼠大脑发育感染鼠巨细胞病毒（MCMV）与神经细胞损失。结合末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）技术和免疫组化染色，3.8%的TUNEL阳性细胞与神经元特异性烯醇化酶的抗体双重染色，而没有TUNEL阳性细胞与MCMV的立即早期和早期病毒抗原的抗体染色。此外，TUNEL阳性细胞的分布模式与原位DNA-DNA杂交检测到的病毒DNA阳性细胞的分布模式不同。超过30%的TUNEL阳性细胞用对小胶质细胞/巨噬细胞特异性的F4/80抗体双重染色，其有时肿胀，推测是神经元凋亡细胞吞噬的结果。在原代神经元培养物中，MCMV感染抑制了通过血清剥夺或谷氨酸处理诱导的细胞凋亡。双染色法也证实了病毒感染的神经元培养物中没有诱导细胞凋亡。这些结果表明，MCMV感染诱导未感染的神经元细胞凋亡，可能是通过间接机制，凋亡细胞被吞噬的小胶质细胞/巨噬细胞。病毒感染诱导和阻断神经细胞凋亡可能对先天性CMV感染引起的脑形态和功能障碍具有重要意义。
Cytomegalovirus (CMV) is the most common cause of congenital infection, resulting in birth defects such as microcephaly. In this study, we found that apoptosis is induced in the developing mouse brain infected with murine cytomegalovirus (MCMV) in an association with neuronal cell loss. With the combination of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique and immunohistochemical staining, 3.8% of the TUNEL-positive cells were double-stained with the antibody to neuron-specific enolase, while none of the TUNEL-positive cells were stained with antibodies to the immediate early and early viral antigens of MCMV. Furthermore, distribution pattern of the TUNEL-positive cells was different from that of viral DNA-positive cells detected by the in situ DNA-DNA hybridization. More than 30% of the TUNEL-positive cells were double-stained with the F4/80 antibody specific for microglia/macrophages, which were sometimes swollen, presumably the consequence of engulfment of the neuronal apoptotic cells. In the primary neuronal cultures, MCMV infection inhibited the induction of apoptosis either by serum deprivation or by glutamate treatment. It was also confirmed by the double-staining method that apoptosis was not induced in the viral-infected neuronal cultures. These results suggest that MCMV infection induces apoptosis in non-infected neuronal cells, presumably by indirect mechanisms, and that apoptotic cells are engulfed by microglia/macrophages. The induction and blocking of neuronal apoptosis by viral infection may be important for morphological and functional brain disorders in the congenital CMV infection.