Cellular prion protein prevents brain damage after encephalomyocarditis virus infection in mice
Cellular prion protein prevents brain damage after encephalomyocarditis virus infection in mice
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DOI：
10.1007/s00705-008-0086-x
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发表时间：
2008-06-01
影响因子：
2.7
通讯作者：
Onodera, T.
中科院分区：
文献类型：
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作者：
Nasu-Nishimura, Y.;Taniuchi, Y.;Onodera, T.
细胞朊病毒蛋白 (PrP(C)) 是一种通常与神经元相关的细胞表面糖蛋白，也在其他细胞类型（例如神经胶质细胞和淋巴细胞）中表达。为了进一步阐明PrP（C）的这些作用，野生型朊病毒蛋白基因（Prnp（+/+））小鼠和Prnp缺陷（Prnp（-/-））小鼠通过颅内途径感染脑心肌炎病毒B变体（EMCV-B）。 EMCV-B 在体内引起脑炎和细胞凋亡。组织病理学研究表明，感染 600 pfu EMCV-B 的 Prnp(+/+) 小鼠比 Prnp(-/-) 小鼠表现出更严重的炎症细胞浸润，并伴有海马周围小胶质细胞的更高活化；也就是说，这两个系小鼠的脑病毒滴度没有差异。脑标本的末端脱氧核苷酸转移酶（TdT）介导的dUTP、缺口末端标记（TUNEL）染色显示，CA1海马锥体细胞中Prnp（-/-）小鼠的凋亡神经元数量多于Prnp（+/+）小鼠。基于所有这些发现，PrP(C)可能在体内诱导炎症和抑制细胞凋亡中发挥一定作用。
Cellular prion protein (PrP(C)), a cell-surface glycoprotein normally associated with neurons, is also expressed in other cell types such as glia and lymphocytes. To further elucidate these roles of PrP(C), wild-type prion protein gene (Prnp(+/+)) mice and Prnp-deficient (Prnp(-/-)) mice were infected with encephalomyocarditis virus B variant (EMCV-B) via an intracranial route. EMCV-B causes encephalitis and apoptotic cell death in vivo. Histopathological studies revealed that Prnp(+/+) mice infected with 600 pfu of EMCV-B showed more severe infiltration of inflammatory cells, accompanied by higher activation of microglia cells around the hippocampus, than Prnp(-/-) mice; viz., no differences in the brain virus titer between these two lines of mice. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP, nick end-labeling (TUNEL) staining of the brain specimens revealed that the CA1 hippocampal pyramidal cells showed a larger number of apoptotic neurons in Prnp(-/-) than Prnp(+/+) mice. Based on all these findings, PrP(C) may play certain roles in the induction of inflammation and inhibition of apoptosis in vivo.