Measles virus spreads in rat hippocampal neurons by cell-to-cell contact and in a polarized fashion

Measles virus spreads in rat hippocampal neurons by cell-to-cell contact and in a polarized fashion
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DOI:
10.1128/jvi.76.11.5720-5728.2002
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发表时间:
2002-06-01
影响因子:
5.4
通讯作者:
Naim, HY
Naim, HY
中科院分区:
医学2区
文献类型:
--
作者:
Ehrengruber, MU;Ehler, E;Naim, HY

文献摘要

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麻疹病毒(MV)可感染中枢神经系统,在极少数情况下,会引起亚急性硬化性全脑炎,其特征是神经元进行性变性。利用表达绿色荧光蛋白的MV,在培养的大鼠海马切片中研究MV在神经元中的传递途径。 MV 感染海马神经元,并以逆行方式单向传播,从 CA1 锥体细胞传播到 CA3 锥体细胞,再从那里传播到齿状回。感染的传播取决于细胞间的接触,并且在没有任何可检测到的感染性颗粒释放的情况下发生。病毒蛋白在逆行MV传播中的作用是通过研究它们在受感染的锥体细胞中的分类来确定的。 MV 糖蛋白、融合蛋白 (F) 和血凝素 (H)、基质蛋白 (M) 和磷蛋白 (P)(病毒核糖核蛋白复合物的一部分)均被分选至树突。虽然 M、P 和 H 蛋白更多地保留在细胞内,但 F 蛋白定位于受感染细胞表面突出的脊柱型结构域。检测到的 MV 蛋白定位表明局部微融合事件可能是由突触接触位点的 F 蛋白介导的,并且与 MV 感染逆行传播的机制一致。
Measles virus (MV) can infect the central nervous system and, in rare cases, causes subacute sclerosing panencephalitis, characterized by a progressive degeneration of neurons. The route of MV transmission in neurons was investigated in cultured rat hippocampal slices by using MV expressing green fluorescent protein. MV infected hippocampal neurons and spread unidirectionally, in a retrograde manner, from CA1 to CA3 pyramidal cells and from there to the dentate gyrus. Spreading of infection depended on cell-to-cell contact and occurred without any detectable release of infectious particles. The role of the viral proteins in the retrograde MV transmission was determined by investigating their sorting in infected pyramidal cells. MV glycoproteins, the fusion protein (F) and hemagglutinin (H), the matrix protein (M), and the phosphoprotein (P), which is part of the viral ribonucleoprotein complex, were all sorted to the dendrites. While M, P, and H proteins remained more intracellular, the F protein localized to prominent, spine-type domains at the surface of infected cells. The detected localization of MV proteins suggests that local microfusion events may be mediated by the F protein at sites of synaptic contacts and is consistent with a mechanism of retrograde transmission of MV infection.