每年流感病毒都造成全球數百萬人的感染，在臨床上，流感病毒感染除了可以觀察到一些呼吸道的症狀，嚴重的話會造成肺炎或導致死亡。流感病毒表面具有血球凝集素(Hemagglutinin，HA)，在頂端部分具有一個受體結合位置，主要是辨識宿主細胞表面的唾液酸(N-acetyl Neuraminic Acid, Neu5Ac)受體進而感染宿主。在H1病毒中，受體結合位置上的這些氨基酸是具有高度保留性的，有許多文獻指出，這些氨基酸決定了病毒對於α2-3 和 α2-6結構的唾液酸的親和力。在2009年4月，墨西哥爆發新流感H1N1(pandemic influenza H1N1)疫情，而且很快地經由人傳人的方式傳播到全世界。在他人研究中指出，這株病毒是由豬、禽、人流感病毒重組而形成的，其中HA基因是來自豬流感病毒。經由序列分析，我們發現在新流感與季節性流感病毒的受體結合位置有許多氨基酸差異的位點，所以我們想要研究這些差異對於新流感與季節性流感病毒的受體結合能力之影響。我們利用受體結合實驗(receptor binding assay)去觀察新流感與季節性流感病毒對於galactose或lactosamine以α2-3結構連結的唾液酸受體(Neu5Acα2-3Gal or Neu5Acα2-3LacNAc)和galactose或lactosamine以α2-6結構連結的唾液酸受體(Neu5Acα2-6Gal or Neu5Acα2-6LacNAc)的親和力。我們發現新流感病毒對受體結合的能力和季節性流感是相似的，尤其是對於較長的醣類(Neu5Acα2-3LacNAc和Neu5Acα2-6LacNAc)。之後，我們在與細胞結合的平台觀察新流感與季節性流感的結合能力，也發現結果與glycan的結合有相關性。除此之外，我們也去探討它們之間的神經胺酸酶(Neuraminidase，NA)的活性，NA主要在病毒複製完後切除它和細胞表面的連結，我們看到新流感具有高NA活性。因此，我們認為新流感的爆發與它具有和季節性流感相若的受體結合能力再加上高NA活性的平衡有關。這些結果有助於我們更了解流感病毒的感染與傳播。

Influenza virus causes epidemics worldwide that affect millions of people annually. Clinical spectrums of influenza virus infections range from mild respiratory tract infection to severe pneumonia and death. The membrane hemagglutinin (HA) glycoprotein is the receptor-binding protein that targets to cell surface receptors containing sialic acid (N-acetyl Neuraminic Acid, Neu5Ac). Amino acids that comprise this receptor binding site is a pocket located on the distal end of HA molecule and are highly conserved among numerous H1 influenza viruses. Numerous reports have demonstrated that amino acids of receptor-binding domain of HA protein contributes to its relative binding affinities for α2-3 or α2-6 linked receptors. In April 2009, the first outbreak of pandemic influenza H1N1 in Mexico spreaded rapidly across the world via human-to-human transmission. It has been reported that reassorted pandemic H1N1 virus containing HA gene originated from swine and other RNA segments from swine, avian and human. Our sequence analysis revealed a lot of amino acid variations in receptor-binding sites between pandemic and seasonal H1N1 viruses. To investigate whether pandemic H1N1 viruses display differential receptor binding ability, we first determined the binding affinity of seasonal and pandemic H1N1 for N-acetyl neuraminic acid linked to galactose or lactosamine by α2-3 linkage (Neu5Acα2-3Gal or Neu5Acα2-3LacNAc) or by α2-6 linkage (Neu5Acα2-6Gal or Neu5Acα2-6LacNAc) by receptor binding assay. We found that the receptor binding ability of pandemic H1N1 is close to binding ability of seasonal H1N1, especially the longer glycan (Neu5Acα2-3LacNAc & Neu5Acα2-6LacNAc). In addition, we performed the binding assay of pandemic and seasoanal H1N1 to cells (MDCK, A549, DF-1 & TWO1), and found that the binding profiles were similar and correlated with glycan binding result. Furthermore, we examined their NA activity which is related to virus releasing from the cell surface, pandemic H1N1 showed higher NA activity. In conclusions, we demonstrate that pandemic H1N1 with similar binding affinity as seasonal H1N1 and the higher NA activity may be responsible for higher transmission which results in 2009 pandemic and afterward. These findings may help us in understanding the influenza virus infection and transmission.

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