Borna Disease Virus Requires Cholesterol in both Cellular Membrane and Viral Envelope for Efficient Cell Entry
Borna Disease Virus Requires Cholesterol in both Cellular Membrane and Viral Envelope for Efficient Cell Entry
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DOI：
10.1128/jvi.02206-08
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发表时间：
2009-03-15
影响因子：
5.4
通讯作者：
de la Torre, Juan C.
中科院分区：
文献类型：
--
作者：
Clemente, Roberto;de Parseval, Aymeric;de la Torre, Juan C.
博纳病病毒（BDV）是单单病毒目博纳病毒科的原型成员，为研究病毒在中枢神经系统（CNS）内的持久性和相关脑部疾病提供了一个重要模型。BDV具有高度的神经嗜性，并通过受体介导的内吞作用进入靶细胞，这是一个由病毒表面糖蛋白(G)介导的过程，但决定BDV细胞在中枢神经系统内嗜性的细胞因子和途径大多尚不清楚。胆固醇通过其对不同病毒过程的影响影响病毒感染，包括复制、出芽和细胞进入。在这项工作中，我们发现BDV的细胞进入，而不是复制和基因表达，被细胞胆固醇水平的消耗大大抑制。BDV G介导的BDV易感细胞的附着与胆固醇无关，但G定位于质膜上的脂筏（LR）。LR的结构和功能严重依赖于胆固醇，因此，胆固醇消耗导致的LR结构完整性和功能受损可能抑制了BDV细胞内化的初始阶段。此外，我们还表明病毒包膜胆固醇是BDV传染性所必需的。
Borna disease virus (BDV), the prototypic member of the family Bornaviridae within the order Mononegavirales, provides an important model for the investigation of viral persistence within the central nervous system (CNS) and of associated brain disorders. BDV is highly neurotropic and enters its target cell via receptor-mediated endocytosis, a process mediated by the virus surface glycoprotein (G), but the cellular factors and pathways determining BDV cell tropism within the CNS remain mostly unknown. Cholesterol has been shown to influence viral infections via its effects on different viral processes, including replication, budding, and cell entry. In this work, we show that cell entry, but not replication and gene expression, of BDV was drastically inhibited by depletion of cellular cholesterol levels. BDV G-mediated attachment to BDV-susceptible cells was cholesterol independent, but G localized to lipid rafts (LR) at the plasma membrane. LR structure and function critically depend on cholesterol, and hence, compromised structural integrity and function of LR caused by cholesterol depletion likely inhibited the initial stages of BDV cell internalization. Furthermore, we also show that viral-envelope cholesterol is required for BDV infectivity.