流行性感冒病毒(Influenza Virus)是一種常見的傳染性致病原，屬於正黏液病毒科(Orthomyxoviridae family)，其基因體是由八段的負股RNA組成，有可能因為突變或不同病毒株間基因互換而造成流感病毒的大流行。在流感病毒的八段RNA基因當中，M及NP基因會合成基質蛋白、M2蛋白及核蛋白，這些蛋白在流感病毒的複製上扮演很重要的角色。在本篇論文中我們分析了1998年到2007年6月在台灣地區流行的A與B型流感病毒的M及NP基因，觀察這兩個基因的演化情形及胺基酸的改變。這4個基因都有逐年的變化，不同型別間的M或NP基因沒有互換。在A型流感的M1蛋白當中，大多數的胺基酸改變都發生在C端上， M1蛋白的N端則是非常的穩定；M2蛋白的胺基酸改變多位於細胞質內的部份（Cytoplasmic tail），而與Amantadine抗藥性有關的胺基酸改變，S31N，在2005年之後大量出現，顯示近年來對Amantadine有抗藥性流感病毒大量增加。在A型流感的核蛋白中，胺基酸的改變主要集中在RNA結合位（RNA binding site）及NP與PB2蛋白或NP蛋白間自我連結的結合位(NP2區域)，而NP間自我連結的結合位(NP1區域)則是較穩定，僅有三個位置有短暫的胺基酸改變。在B型流感病毒中，其M1蛋白非常的穩定，在10年中僅僅有一個胺基酸的改變；而BM2蛋白當中則有5個位置有胺基酸的改變，都位於細胞質內的部份（Cytoplasmic Tail）。B型流感病毒的核蛋白當中有6個胺基酸位置的變化，不過和其他的基因一樣，大多數的改變都是變成性質相近的胺基酸。以上結果提供了流行於台灣的流感病毒的M及NP基因在過去10年間的變化，可以提供台灣及全球對於流行性感冒監控更近一步的資訊。

Influenza virus belongs to Orthomyxoviridae family, its genome consists of 8 negative sense RNA genes. The antigentic drift and reassortment of influenza genome may cause epidemics and pandemics. Among these 8 segments of influenza genes, the Matrix (M) and nucleoprotein (NP) genes encode the Matrix protein (M1), membrane protein (M2) and the nucleoprotein, which play important roles in influenza replication. Here we analyzed the evolution of these two genes and monitor the amino acid changes of the proteins they encode. All the influenza isolates were collected in Taiwan during 1998 to 2007. Reassortments were not observed among these 4 genes. Amino acid substitutions within matrix protein of influenza A virus were observed mostly in RNP binding domain, however, the RNA binding domain of matrix protein was pretty conserved. For the M2 protein, most of the amino acid substitutions were located in cytoplasmic tail, and the amino acid substitution known for amantadine resistance was observed in most of influenza isolated after 2005. Most of the amino acid substitutions in nucleoprotein of influenza A virus were located in the RNA binding domain NP-PB2 interaction domain and NP-NP interaction domain (the NP-2 region). The NP-1 region was quite conserved, only 3 amino acid substitutions were observed. In the influenza B viruses, the matrix (M1) protein was extremely conserved that only one amino acid change was observed. There were 5 amino acid substitutions in the BM2 protein of influenza B virus observed, all of them were located in cytoplasmic domain of membrane protein (BM2). As for the nucleoprotein of influenza B virus, 6 amino acid substitutions were observed. Same as other substitutions in other proteins, most of these changes were substituted by amino acids with similar properties. These results provide information of the evolution in the M and the NP genes of influenza A and B viruses in Taiwan last decade, and may contribute to the surveillance of influenza viruses in Taiwan and in the world.

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