Department of Microbiology, Faculty of Science, Mahidol University, 272 Rama 6 Road, Ratchatewee, Bangkok 10400, Thailand.
J Gen Virol. 2011 Feb;92(Pt 2):307-14. doi: 10.1099/vir.0.025973-0. Epub 2010 Oct 27.
Virus evolution facilitates the emergence of viruses with unpredictable impacts on human health. This study investigated intra-host variations of the receptor-binding domain (RBD) of the haemagglutinin (HA) gene of the avian H5N1 viruses obtained from the 2004 and 2005 epidemics. The results showed that the mutation frequency of the RBD ranged from 0.3 to 0.6 %. The mutations generated one consensus and several minor populations. The consensus population of the 2004 epidemic was transmitted to the 2005 outbreak with increased frequency (39 and 45 %, respectively). Molecular dynamics simulation was applied to predict the significance of the variants. The results revealed that the consensus sequence (E218K/V248I) interacted unstably with sialic acid (SA) with an α2,6 linkage (SAα2,6Gal). Although the mutated K140R/E218K/V248I and Y191C/E218K/V248I sequences decreased the HA binding capacity to α2,3-linked SA, they were shown to bind α2,6-linked SA with increased affinity. Moreover, the substitutions at aa 140 and 191 were positive-selection sites. These data suggest that the K140R and Y191C mutations may represent a step towards human adaptation of the avian H5N1 virus.
病毒进化促进了具有不可预测的人类健康影响的病毒的出现。本研究调查了 2004 年和 2005 年流行期间从宿主中获得的禽流感 H5N1 病毒血凝素 (HA) 基因受体结合域 (RBD) 的内部变异。结果表明，RBD 的突变频率为 0.3%至 0.6%。突变产生了一个共识和几个小种群。2004 年流行的共识种群以增加的频率传播到 2005 年的爆发（分别为 39%和 45%）。应用分子动力学模拟预测了变体的意义。结果表明，共识序列（E218K/V248I）与唾液酸（SA）以α2,6 键（SAα2,6Gal）不稳定地相互作用。尽管突变的 K140R/E218K/V248I 和 Y191C/E218K/V248I 序列降低了 HA 与α2,3 连接的 SA 的结合能力，但它们显示与α2,6 连接的 SA 的结合亲和力增加。此外，aa140 和 191 的取代是正选择位点。这些数据表明，K140R 和 Y191C 突变可能代表禽流感 H5N1 病毒向人类适应的一步。
