H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion
H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion
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DOI：
10.1128/jvi.02332-15
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发表时间：
2016-02-01
影响因子：
5.4
通讯作者：
Matrosovich, Mikhail
中科院分区：
文献类型：
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作者：
Baumann, Jan;Kouassi, Nancy Mounogou;Matrosovich, Mikhail
H1N1 欧亚禽类猪 (EAsw) 流感病毒源自禽 H1N1 病毒。为了表征病毒在禽类到猪的适应过程中血凝素 (HA) 膜融合活性的潜在变化，我们研究了在猪体内传播的头几年分离的 EAsw 病毒以及密切相关的当代野生水禽 H1N1 病毒。与禽病毒相比，猪病毒对 MDCK 细胞中溶酶体试剂 NH4Cl 的中和不太敏感，溶血活性的最适 pH 值较高，并且在酸性 pH 下稳定性较差。发现 HA 中的八个氨基酸取代可将 EAsw 病毒与其假定的禽类前体分开；四个取代 - T49(2)S、N72(2)D、R75(2)K 和 S113(2)F - 位于已知在酸诱导的 HA 构象转变中发挥作用的 HA2 亚基的结构区域。我们还研究了细胞表达的 HA 蛋白在低 pH 值诱导的合胞体形成，发现 1918 年、1957 年、1968 年和 2009 年大流行病毒的 HA 需要比代表性 EAsw 病毒的 HA 更低的 pH 值来进行融合诱导。我们的数据表明，禽 H1N1 病毒向猪的传播伴随着 HA 的构象稳定性和融合促进活性的变化。我们的结论是，HA 独特的宿主决定的融合特征可能代表了流感病毒从禽到猪和猪到人传播的障碍。
The H1N1 Eurasian avian-like swine (EAsw) influenza viruses originated from an avian H1N1 virus. To characterize potential changes in the membrane fusion activity of the hemagglutinin (HA) during avian-to-swine adaptation of the virus, we studied EAsw viruses isolated in the first years of their circulation in pigs and closely related contemporary H1N1 viruses of wild aquatic birds. Compared to the avian viruses, the swine viruses were less sensitive to neutralization by lysosomotropic agent NH4Cl in MDCK cells, had a higher pH optimum of hemolytic activity, and were less stable at acidic pH. Eight amino acid substitutions in the HA were found to separate the EAsw viruses from their putative avian precursor; four substitutions-T49(2)S, N72(2)D, R75(2)K, and S113(2)F-were located in the structural regions of the HA2 subunit known to play a role in acid-induced conformational transition of the HA. We also studied low-pH-induced syncytium formation by cell-expressed HA proteins and found that the HAs of the 1918, 1957, 1968, and 2009 pandemic viruses required a lower pH for fusion induction than did the HA of a representative EAsw virus. Our data show that transmission of an avian H1N1 virus to pigs was accompanied by changes in conformational stability and fusion promotion activity of the HA. We conclude that distinctive host-determined fusion characteristics of the HA may represent a barrier for avian-to-swine and swine-to-human transmission of influenza viruses.