School of Life Sciences, University of Science and Technology of China, Hefei 230026, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.
Cell Rep. 2019 Nov 19;29(8):2217-2228.e5. doi: 10.1016/j.celrep.2019.10.047.
Since 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1,600 human infections, posing a threat to public health. An emerging concern is whether H7N9 AIVs will cause pandemics among humans. Molecular analysis of hemagglutinin (HA), which is a critical determinant of interspecies transmission, shows that the current H7N9 AIVs are still dual-receptor tropic, indicating limited human-to-human transmission potency. Mutagenesis and structural studies reveal that a G186V substitution is sufficient for H7N9 AIVs to acquire human receptor-binding capacity, and a Q226L substitution would favor binding to both avian and human receptors only when paired with A138/V186/P221 hydrophobic residues. These data suggest a different evolutionary route of H7N9 viruses compared to other AIV-subtype HAs.
自 2013 年以来，H7N9 禽流感病毒（AIVs）已导致 1600 多人感染，对公众健康构成威胁。一个新出现的问题是，H7N9 AIVs 是否会在人类中引发大流行。对血凝素（HA）的分子分析表明，HA 是决定种间传播的关键决定因素，目前的 H7N9 AIVs 仍然具有双受体嗜性，这表明其在人与人之间的传播能力有限。突变和结构研究表明，G186V 取代足以使 H7N9 AIVs 获得人类受体结合能力，而只有当与 A138/V186/P221 疏水性残基配对时，Q226L 取代才有利于与禽源和人源受体结合。这些数据表明，与其他 AIV 亚型的 HA 相比，H7N9 病毒的进化途径不同。
