Borna disease virus glycoprotein is required for viral dissemination in neurons
Borna disease virus glycoprotein is required for viral dissemination in neurons
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DOI：
10.1128/jvi.77.22.12222-12231.2003
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发表时间：
2003-11-01
影响因子：
5.4
通讯作者：
Gonzalez-Dunia, D
中科院分区：
文献类型：
--
作者：
Bajramovic, JJ;Münter, S;Gonzalez-Dunia, D
博尔纳病病毒是一种非节段性负链RNA病毒，其嗜性为神经元。感染BDV会导致多种动物的神经系统疾病。尽管已知病毒在神经元之间传播，但在受感染动物的大脑中从未见过组装的病毒颗粒。这导致了BDV以无包膜核糖核蛋白(RNP)而不是包膜病毒颗粒的形式传播的假设。我们利用原代培养的大鼠海马神经元来评估BDV的神经元传播是否需要病毒包膜糖蛋白(GP)。我们发现，在体外感染后，BDV在该系统中有效地复制和传播。尽管病毒传播迅速，但在培养物中检测到的传染性病毒颗粒很少。然而，针对BDV-gp的中和抗体抑制了BDV的传播。此外，通过抑制Furin介导的糖蛋白切割来干扰BDV-gp的加工，阻止了病毒的传播。最后，针对BDV-gp mRNA的反义多肽核酸治疗抑制了BDV的传播，标志着BDV-gp成为抗BDV的一个有吸引力的靶点。综上所述，我们的结果表明，BDV-gp的表达和正确处理是BDV在原代培养的大鼠海马神经元中传播所必需的，这证明了BDV-gp是以无包膜RNP的形式从神经元传播到神经元的假设。
Borna disease virus (BDV) is a nonsegmented negative-strand RNA virus with a tropism for neurons. Infection with BDV causes neurological diseases in a wide variety of animal species. Although it is known that the virus spreads from neuron to neuron, assembled viral particles have never been visualized in the brains of infected animals. This has led to the hypothesis that BDV spreads as nonenveloped ribonucleoproteins (RNP) rather than as enveloped viral particles. We assessed whether the viral envelope glycoprotein (GP) is required for neuronal dissemination of BDV by using primary cultures of rat hippocampal neurons. We show that upon in vitro infection, BDV replicated and spread efficiently in this system. Despite rapid virus dissemination, very few infectious viral particles were detectable in the culture. However, neutralizing antibodies directed against BDV-GP inhibited BDV spread. In addition, interference with BDV-GP processing by inhibiting furin-mediated cleavage of the glycoprotein blocked virus spread. Finally, antisense treatment with peptide nucleic acids directed against BDV-GP mRNA inhibited BDV dissemination, marking BDV-GP as an attractive target for antiviral therapy against BDV. Together, our results demonstrate that the expression and correct processing of BDV-GP are necessary for BDV dissemination in primary cultures of rat hippocampal neurons, arguing against the hypothesis that the virus spreads from neuron to neuron in the form of nonenveloped RNP.