Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control & Prevention, 1600 Clifton Road, MS-G16, Atlanta, GA 30333, USA.
Virology. 2011 Apr 25;413(1):139-47. doi: 10.1016/j.virol.2011.02.015. Epub 2011 Mar 23.
Although H5N1 influenza viruses have been responsible for hundreds of human infections, these avian influenza viruses have not fully adapted to the human host. The lack of sustained transmission in humans may be due, in part, to their avian-like receptor preference. Here, we have introduced receptor binding domain mutations within the hemagglutinin (HA) gene of two H5N1 viruses and evaluated changes in receptor binding specificity by glycan microarray analysis. The impact of these mutations on replication efficiency was assessed in vitro and in vivo. Although certain mutations switched the receptor binding preference of the H5 HA, the rescued mutant viruses displayed reduced replication in vitro and delayed peak virus shedding in ferrets. An improvement in transmission efficiency was not observed with any of the mutants compared to the parental viruses, indicating that alternative molecular changes are required for H5N1 viruses to fully adapt to humans and to acquire pandemic capability.
虽然 H5N1 流感病毒已导致数百人感染，但这些禽流感病毒尚未完全适应人类宿主。其在人类中无法持续传播的原因部分可能是由于其类似禽类的受体偏好。在这里，我们在两种 H5N1 病毒的血凝素（HA）基因中引入了受体结合结构域突变，并通过糖基化微阵列分析评估了受体结合特异性的变化。通过体外和体内评估了这些突变对复制效率的影响。尽管某些突变改变了 H5HA 的受体结合偏好，但拯救的突变病毒在体外的复制能力降低，在雪貂中的病毒峰值排出时间延迟。与亲本病毒相比，任何突变体都没有观察到传播效率的提高，这表明 H5N1 病毒要完全适应人类并获得大流行能力还需要其他分子变化。
