流行性感冒病毒HA蛋白質序列的物理化學性質分析

Physicochemical Analysis of Flu Hemagglutinin Sequence

陳彥州(ch'ên yen chou)

指導教授 ： 張培均

亞洲大學/資訊學院/生物資訊學系碩士班/碩士(2007年)

摘要

1918 年，流行性感冒突然嚴重爆發，在全世界有二千萬到四千萬人因為感 染流行性感冒疾病而死亡，造成如此高感染力的原因始終不明，因此James Stevens 和Scripps 學院的Ian Wilson 在La Jolla 開始著手研究採自阿拉斯加受難 者的屍體組織，希望能夠找出原因，他們找出病毒表面蛋白hemagglutinin (HA) 的序列並分析其結構，結果顯示，它跟感染鳥的流行性感冒病毒較接近較有關係。 對於流行性感冒病毒來說，HA 蛋白是非常重要的，因為它結合到人類的肺 細胞表面受器，此時，HA 會改變形態幫助病毒的膜與宿主融合，整個過程在分 子層次上是物理化學的交互作用。1918 年造成異常高的傳染性和死亡率的HA 蛋 白，在結構上有兩個特別突出的特徵異於一般：(1)一般受器結合位置的範圍是 狹小的，然而1918 年流行性感冒病毒的HA 蛋白卻以一個氨基酸突變，使結合位 置稍微的變大，這可能會增加傾向於對人類細胞的感染。(2)有兩個之前未被查 覺的鹼性小片段(histidine rich)，當病毒融入細胞膜時，可能會提高HA 的感染 性，其中一個小片段被發現只有在感染鳥的病毒種類中才有。 根據這些線索，我們推論流行性感冒病毒的感染對象，以及禽流感感染人的 可能性，應該跟它的HA蛋白質序列所具有的物理化學性質，有很密切的關係。 因此，我們利用資料探勘的方法，找出流行性感冒病毒的HA蛋白序列中，感染 人與禽類所具備的物理化學性質特徵差異。我們從公開的資料庫 (http://www.flu.lanl.gov/)中搜集各種流感病毒的HA蛋白質序列，並分別針對序列 上氨基酸的酸鹼性、凡得瓦體積、表面積與疏水性，做與感染事件有關的物理化 學性質特徵分析，並找出了一些感染人與禽類的差異點。這些特徵差異點，有助 於將來針對病毒的感染以及禽流感感染人類的可能性，發展有效的防制方法。

關鍵字

流行性感冒

並列摘要

In 1918, the flu suddenly broke out seriously, 20 million to 40 million people die in infection. The cause of high appeal is still unclear. For the sake of this reason,James Stevens and Ian Wilson who is the faculty of the institute of Scripps studied the structural characters of hemagglutinin (HA) protein that sampled from the victim person in the Alaska.
The result revealed that the flu closely relative to the epidemic influenza virus which infects the bird.The HA protein is very important in the event of flu infection,because it bind to the receptor on the cellular surface of human lung specifically, and bring about membrane fusion by the change of conformation. All of the processes are physiochemical interactions in the molecular level.
There are two significant physiochemical features for the flu infection which broke out in 1918 may responsible to the high infection and mortality: (1) In general, the size of binding position is narrow, but becoming larger by one amino acid change on the binding position in the flu of 1918, that apt to promote the infection to human. (2) Two histidine-rich segments with basicity may promote the membrane fusion in the infection process.One of the two segments found only in avin flu.
According to these clues, we assumed that the infective host and the probability of cross-species infection could be determined by the physiochemical properties of residues in the HA protein sequence.
So, we utilized the method of data mining to discover the significant differences in the HA protein sequences between avin and IV human flu. All the HA protein sequences was collected from public database (http://www.flu.lanl.gov/).
The physiochemical properties of residues we studied including hydrophobicity, Van der Waals volume, surface area, and acid-base property. Some important characters have discovered, that may have big help to develop the preventive strategy for the flu infection and cross-species infection, in the future.

並列關鍵字

Physicochemical

參考文獻

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