流行性感冒病毒(流感病毒) 之感染在老年人及小孩中常造成極高的罹病率及死亡率。是否能成功地使用疫苗來控制流感病毒之感染主要決定於當季所流行的病毒株以及流感病毒感染之季節型態。雖然A型及B型流感病毒之感染在溫帶地區流行的季節主要是在冬季，不過在台灣它們依然可活躍於春天、夏天及早秋。Amantadine 這個藥物主要是用來治療及預防A型流感病毒之感染，倘若產生具有抗amantadine 之A型流感病毒株，其可能會引起大規模之流行。因此，對A型流感病毒對此藥物之抗藥性之了解有助於對流感病毒之流行的預防提供良好的線索。所以本研究的目地包括(1) A型及B型流感病毒的分子流行病學分析(2) A 型流感病毒H1N2亞型的出現率(3) 監測A型流感病毒中產生amantadine 抗藥性之比例，以了解南台灣流病毒流行之情形。
　　我們所分析的病毒株包括來自1999 年至2004 年南台灣A型流感病毒(H3N2 及H1N1) 及B型流感病毒等。在分析H3、H1A型流感病毒的HA (Hemagglutinin, HA)基因及抗原性之變化顯示，其HA1的區域與prototype之疫苗株相比不管在核? 酸或是胺基酸的變化中呈現出逐年連續性漂變(drift)的情形。2002 年三月至2004 年的H3病毒株與疫苗株(A/Panama/2007/99) 相比，發現於B抗原決定位中有一至三個胺基酸陸續被取代的病毒株；而這三個胺基酸被取代之病毒株在分子流行病學的分析中與疫苗株(A/Fujian/411/02) (WHO 2004/2005 北半球所推薦之疫苗株)是屬於同一個clade。此結果顯示福建株早在2003 年3月即在南台灣出現。在1999/2000 季節的H1病毒株(A/New Caledonia/20/99-like) 中，與疫苗株北京株(A/Beijing/262/95)相比其胺基酸分別在3個抗原決定位(Sa, Sb, Ca)產生改變，這被認為是那個季節造成台灣H1大流行的原因。B型流感病毒方面，1998-2000 年間病毒株均屬於Yamagata 系源，但自2001 年3月我們開始發現流行於1980 年代的B/Victoria/2/87 系源之病毒株。此外，發現自2002 年4月之部份病毒株其HA與NA(Neuraminidase, NA) 之間有來自Victoria 及Yamagata 不同系源之基因重組(genetic reassortmant)的現象，所測試之2002 年的病毒株中重組病毒佔46% (5/11)。對基因重組之B型流感病毒做HA 的基因分析，發現它們皆來自B/Victoria/2/87 系源的一個分支且與B/Hong Kong/1351/02 疫苗株相類似，而其NA基因則來自Yamagata 系源。另外從我們所分析的病毒株中，顯示到目前為止南台灣還未出現H1N2 病毒株。此外，1999 年至2002 年間我們利用了PCR-RFLP 方法偵測53 株A型流感病毒株(20 株H3N2、33 株H1N1)之amatadine 抗藥性之能力。由PCR-RFLP之結果發現雖然有兩株病毒株為具抗藥性之型態，不過經由序列之分析發現其突變的位置是位於第3個核? 乾酸屬於nonsense的突變。以上這些結果針對南台灣流感病毒株有深一層的了解，並且可供我們在全球監控流感病毒的資訊上提供進一步之訊息。

　　Infection with influenza viruses can cause severe morbidity and mortality in the elderly and children. Successful application of vaccine for influenza control in a particular region depends on the circulating strains and seasonal pattern of influenza infection. Although infections with influenza virus A and B predominate in winter seasons, they were also observed in the spring, summer, and early fall in Taiwan. Amantadine has shown effect in treatment and preventing influenza A virus infections. Amantadine resistant influenza A virus may result in epidemic infection. Therefore, well understanding the variation of influenza viruses can give the clues for viral prophylaxis. In this study, we examined (1) the molecular epidemiology of influenza A and B viruses (2) the occurrence of H1N2 of influenza A virus (3) monitoring the incidence of amantadine resistance influenza A virus in southern Taiwan.
　　The isolates of influenza A (H3N2 and H1N1) and B viruses between 1999 and 2004 from southern Taiwan were used for this study. In the genetic and antigenic analysis in HA (Hemagglutinin, HA) gene of influenza A (H3, H1), the results showed continuous drift of nucleotide and amino acid in the HA1 region increased year by year when compared with the prototype vaccine strains. There were 1, 2, and 3 amino acid substitutions in antigenic site B of H3 isolates found between 2002 March-2004 Jan when compared to A/Panama/2007/99 vaccine strain. The isolates with 3 amino acid changes and A/Fujian/411/02 (WHO 2004/2005 northern hemisphere vaccine strain) belonged to the same clade in the phylogenetic analysis, indicating Fujian-like strains occurrence in southern Taiwan since March 2003. Among 1999/2000 H1 isolates, the amino acid showed changes in the three antigenic sites (Sa, Sb, and Ca1), when compared with A/Beijing/262/95 vaccine strain, which was considered as the reason for the burst outbreak. Most influenza B viruses between 1998 to 2000 belonged to B/Yamagata lineage, since March 2001, B/Victoria/2/87 lineage isolates were identified cocirculating with Yamagata lineage. More interestingly, genetic reassortants of influenza B with different lineage of HA and NA (Neuraminidase, NA) genes were found since April 2002, and 46% (5/11) reassortment virus of 2002 influenza B virus were found. Genetic analysis of the HA gene showed that the B reassortant viruses formed a separate branch from Victoria lineage and were most closely related to B/Hong Kong/1351/02 vaccine strain and NA gene was reassorted from Yamagata lineage. In addition, our study showed lack of H1N2 viruses in Taiwan to date. Furthermore, between 1999 and 2002, fifty-three influenza A viruses isolates (20 H3N2, 33 H1N1) were examined by PCR-RFLP method to screen the single amino acid substitution at position 27, 30 and 31 in the transmembrane domain of the M2 protein in amatadine resistant influenza A viruses. There were two isolates with resistant patterns but the sequence analysis showed nonsense mutations at the third nucleotide. In conclusions, these results provide the better understanding of the influenza viruses in southern Taiwan, and they will serve us as the baseline information for continued worldwide surveillance of influenza viruses.

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