Novel Phylogenetic Algorithm to Monitor Human Tropism in Egyptian H5N1-HPAIV Reveals Evolution toward Efficient Human-to-Human Transmission

Years of endemic infections with highly pathogenic avian influenza (HPAI) A subtype H5N1 virus in poultry and high numbers of infections in humans provide ample opportunity in Egypt for H5N1-HPAIV to develop pandemic potential. In an effort to better understand the viral determinants that facilitate human infections of the Egyptian H5N1-HPAIVvirus, we developed a new phylogenetic algorithm based on a new distance measure derived from the informational spectrum method (ISM). This new approach, which describes functional aspects of the evolution of the hemagglutinin subunit 1 (HA1), revealed a growing group G2 of H5N1-HPAIV in Egypt after 2009 that acquired new informational spectrum (IS) properties suggestive of an increased human tropism and pandemic potential. While in 2006 all viruses in Egypt belonged to the G1 group, by 2011 these viruses were virtually replaced by G2 viruses. All of the G2 viruses displayed four characteristic mutations (D43N, S120(D,N), (S,L)129Δ and I151T), three of which were previously reported to increase binding to the human receptor. Already in 2006–2008 G2 viruses were significantly (p埃及家禽中高致病性禽流感（highly pathogenic avian influenza, HPAI）A型H5N1亚型病毒的地方性流行感染已持续多年，同时人类感染病例数量居高不下，这为H5N1-HPAIV在埃及演化出大流行潜力提供了充足契机。为更深入解析驱动埃及H5N1-HPAIV感染人类的病毒决定簇，我们基于信息谱方法（informational spectrum method, ISM）衍生的新型距离指标开发了一套全新的系统发育算法。该方法可表征血凝素亚基1（hemagglutinin subunit 1, HA1）演化过程中的功能属性，研究发现2009年后埃及境内出现了持续扩增的H5N1-HPAIV G2进化群，该类群获得了新的信息谱（informational spectrum, IS）特征，提示其人类嗜性与大流行潜力均有所增强。2006年埃及境内的所有病毒均隶属于G1群，而到2011年时，G1群病毒几乎已完全被G2群病毒取代。所有G2群病毒均携带4种特征突变：D43N、S120(D,N)、(S,L)129Δ与I151T，其中3种突变此前已被报道可提升病毒对人类受体的结合能力。早在2006–2008年间，G2群病毒便已呈现出显著的（p