Identification of trypsin I as a candidate for influenza A virus and Sendai virus envelope glycoprotein processing protease in rat brain
Identification of trypsin I as a candidate for influenza A virus and Sendai virus envelope glycoprotein processing protease in rat brain
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DOI：
10.1515/bc.2006.062
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发表时间：
2006-04-01
影响因子：
3.7
通讯作者：
Kido, H
中科院分区：
文献类型：
--
作者：
Le, TQ;Kawachi, M;Kido, H
宿主胰蛋白酶样蛋白酶对病毒包膜融合糖蛋白血凝素（HA（0））的细胞外切割是人甲型流感病毒和仙台病毒感染性和致病性的先决条件。常见的流行性甲型流感病毒是嗜肺的，但偶尔会引起脑病或脑炎，尽管大脑中的HA（0）加工酶尚未确定。在寻找大脑加工蛋白酶的过程中，我们在大鼠大脑中鉴定了一种加工酶，该酶可通过感染这些病毒而诱导。纯化的酶在SDS-PAGE上表现出约22 kDa的表观分子量，N-末端氨基酸序列与大鼠胰蛋白酶I的序列一致。其底物特异性和抑制特性与胰蛋白酶I相同。胰蛋白酶I分布的原位杂交和免疫组织化学研究显示，在脑毛细血管，特别是在allocortex，以及在群集的海马神经元细胞中的重存款。纯化的酶有效地加工人A型流感病毒的HA（0）和仙台病毒的融合糖蛋白前体。我们的研究结果表明，胰蛋白酶I在脑内增强病毒增殖的发病机制和进展的流感相关性脑病或脑炎。
Extracellular cleavage of virus envelope fusion glycoprotein hemagglutinin (HA(0)) by host trypsin-like proteases is a prerequisite for the infectivity and pathogenicity of human influenza A viruses and Sendai virus. The common epidemic influenza A viruses are pneumotropic, but occasionally cause encephalopathy or encephalitis, although the HA(0) processing enzyme in the brain has not been identified. In searching for the brain processing proteases, we identified a processing enzyme in rat brain that was inducible by infection with these viruses. The purified enzyme exhibited an apparent molecular mass of approximately 22 kDa on SDS-PAGE and the N-terminal amino acid sequence was consistent with that of rat pancreatic trypsin I. Its substrate specificities and inhibition profiles were the same as those of pancreatic trypsin I. In situ hybridization and immunohistochemical studies on trypsin I distribution revealed heavy deposits in the brain capillaries, particularly in the allocortex, as well as in clustered neuronal cells of the hippocampus. The purified enzyme efficiently processed the HA(0) of human influenza A virus and the fusion glycoprotein precursor of Sendai virus. Our results suggest that trypsin I in the brain potentiates virus multiplication in the pathogenesis and progression of influenza-associated encephalopathy or encephalitis.