Jakubcová L, Hollý J, Varečková E
Acta Virol. 2016 Jun;60(2):121-35. doi: 10.4149/av_2016_02_121.
Influenza A viruses (IAVs) cause acute respiratory infections of humans, which are repeated yearly. Human IAV infections are associated with significant morbidity and mortality and therefore they represent a serious health problem. All human IAV strains are originally derived from avian IAVs, which, after their adaptation to humans, can spread in the human population and cause pandemics with more or less severe course of the disease. Presently, however, the potential of avian IAV to infect humans and to cause the disease cannot be predicted. Many studies are therefore focused on factors influencing the virulence and pathogenicity of IAV viruses in a given host. The virus-host interaction starts by virus attachment via the envelope glycoprotein hemagglutinin (HA) to the receptors on the cell surface. In addition to receptor binding, HA mediates also the fusion of viral and endosomal membranes, which follows the virus endocytosis. The fusion potential of HA trimer, primed by proteolytic cleavage, is activated by low pH in endosomes, resulting in HA refolding into the fusion-active form. The HA conformation change is predetermined by its 3-D structure, is pH-dependent, irreversible and strain-specific. The process of fusion activation of IAV hemagglutinin is crucial for virus entry into the cell and for the ability of the virus to replicate in the host. Here we discuss the known data about the characteristics of fusion activation of HA in relation to IAV virulence and pathogenicity.
甲型流感病毒（IAV）可引发人类急性呼吸道感染，此类感染每年都会反复出现。人类IAV感染会导致显著的发病率和死亡率，因此构成了一个严重的健康问题。所有人类IAV毒株最初都源自禽IAV，这些禽IAV在适应人类后，能够在人群中传播，并引发病程或轻或重的大流行。然而，目前禽IAV感染人类并引发疾病的可能性尚无法预测。因此，许多研究聚焦于影响IAV病毒在特定宿主中毒力和致病性的因素。病毒与宿主的相互作用始于病毒通过包膜糖蛋白血凝素（HA）与细胞表面受体的结合。除了受体结合外，HA还介导病毒膜与内体膜的融合，这一过程发生在病毒内吞之后。经蛋白水解切割引发的HA三聚体的融合潜能，会被内体中的低pH激活，导致HA重折叠成融合活性形式。HA的构象变化由其三维结构预先决定，依赖于pH，是不可逆的且具有毒株特异性。IAV血凝素的融合激活过程对于病毒进入细胞以及病毒在宿主体内复制的能力至关重要。在此，我们讨论关于HA融合激活特性与IAV毒力和致病性相关的已知数据。
