Proteomic profiling reveals that rabies virus infection results in differential expression of host proteins involved in ion homeostasis and synaptic physiology in the central nervous system
Proteomic profiling reveals that rabies virus infection results in differential expression of host proteins involved in ion homeostasis and synaptic physiology in the central nervous system
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DOI：
10.1080/13550280601178226
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发表时间：
2007-01-01
影响因子：
3.2
通讯作者：
Fu, Zhen F.
中科院分区：
文献类型：
--
作者：
Dhingra, Vikas;Li, Xiaqing;Fu, Zhen F.
为了了解狂犬病毒（RV）感染如何导致神经元功能障碍，作者采用蛋白质组学技术来描述宿主对RV感染的反应。在感染野生型RV的小鼠中，参与离子稳态的蛋白的表达发生了改变。H+ atp酶和Na+/K+ atp酶上调，Ca2+ atp酶下调，导致细胞内Na+和Ca2+浓度降低。此外，wt RV感染导致可溶性NSF附着受体蛋白（SNAREs）下调，如α -突触体相关蛋白（SNAP）、含三方基元9 （TRIM9）、syntaxin和pallidin，这些蛋白都参与突触囊泡与突触前膜的对接和融合。结果，在感染了wt RV的小鼠的前突触中观察到突触囊泡的积累。这些数据表明，wt RV感染导致宿主蛋白表达的改变，特别是那些参与离子稳态和突触囊泡与突触前膜对接融合的蛋白表达，这可能导致神经元功能障碍。另一方面，减弱的RV上调了诱导凋亡相关蛋白的表达，这解释了为什么在以往的研究中仅在感染了减弱RV的细胞或动物中观察到凋亡。
To understand how rabies virus (RV) infection results in neuronal dysfunction, the authors employed proteomics tecnology to profile host responses to RV infection. In mice infected with wild-type (wt) RV, the expression of proteins involved in ion homeostasis was altered. H+ ATPase and Na+/K+ ATPase were up-regulated whereas Ca2+ ATPase was down-regulated, which resulted in reduction of the intracellular Na+ and Ca2+ concentrations. Furthermore, infection with wt RV resulted in down-regulation of soluble NSF attachment receptor protiens (SNAREs) such as alpha-synaptosome-associated protein (SNAP), tripartite motif-containing 9 (TRIM9), syntaxin, and pallidin, all of which are involved in docking and fusion of synaptic vesicles to and with presynaptic membrane. As a consequence, accumulation of synaptic vesicles was observed in the prestnapses of mice infected with wt RV. These data demonstrate that infection with wt RV results in alteration of host protein expression, particularly those involved in ion homeostasis and docking and fusion of synaptic vesicles to presynaptic membrane, which may lead to neuronal dysfunction. On the other hand, attenuated RV up-regulated the expression of proteins involved in the induction of apoptosis, explaining why apoptosis is observed only in cells or animals infected with attenuated RV in previous studies.