Kim Jin Il, Lee Ilseob, Park Sehee, Lee Sangmoo, Hwang Min-Woong, Bae Joon-Yong, Heo Jun, Kim Donghwan, Jang Seok-Il, Song Jin-Won, Park Man-Seong
Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul, 136-705, Republic of Korea.
Arch Virol. 2014 Oct;159(10):2559-65. doi: 10.1007/s00705-014-2104-5. Epub 2014 May 14.
The surface glycoprotein hemagglutinin (HA) of influenza virus initiates the infection process by binding to sialic acid receptors on upper respiratory cells in the host. In contrast to avian influenza viruses, which bind to sialic acids connected by an α2-3 linkage to the penultimate galactose, human influenza viruses prefer sialic acids with an α2-6 linkage. Recently, there have been multiple cases of severe human infections associated with an HA D222G mutant influenza virus. In this study, we have investigated the pathogenic effects of the HA D222G substitution in a 2009 pandemic H1N1 virus in mice. Compared with the A/Korea/01/2009 (K/09) virus, the HA D222G mutant showed reduced growth in cells and reduced binding avidity to human and turkey red blood cells. In a BALB/c mouse infection model, infection with the HA D222G mutant virus resulted in less body weight loss when compared to the parental K/09 virus. Altogether, our data suggest that the HA D222G substitution in the K/09 virus might be deleterious to viral fitness.
流感病毒的表面糖蛋白血凝素（HA）通过与宿主上呼吸道细胞中的唾液酸受体结合来启动感染过程。与通过α2-3连接与倒数第二个半乳糖相连的唾液酸结合的禽流感病毒不同，人流感病毒更喜欢具有α2-6连接的唾液酸。最近，出现了多例与HA D222G突变流感病毒相关的严重人类感染病例。在本研究中，我们调查了HA D222G替换对2009年大流行H1N1病毒在小鼠中的致病作用。与A/韩国/01/2009（K/09）病毒相比，HA D222G突变体在细胞中的生长减少，对人和火鸡红细胞的结合亲和力降低。在BALB/c小鼠感染模型中，与亲本K/09病毒相比，感染HA D222G突变病毒导致的体重减轻较少。总之，我们的数据表明，K/09病毒中的HA D222G替换可能对病毒适应性有害。
