Aganovic Amar
Faculty of Engineering Science and Technology, UiT The Arctic University of Norway, Tromsø, Norway.
Front Microbiol. 2023 May 10;14:1190463. doi: 10.3389/fmicb.2023.1190463. eCollection 2023.
The ongoing SARS-CoV-2 pandemic and the influenza epidemics have revived the interest in understanding how these highly contagious enveloped viruses respond to alterations in the physicochemical properties of their microenvironment. By understanding the mechanisms and conditions by which viruses exploit the pH environment of the host cell during endocytosis, we can gain a better understanding of how they respond to pH-regulated anti-viral therapies but also pH-induced changes in extracellular environments. This review provides a detailed explanation of the pH-dependent viral structural changes preceding and initiating viral disassembly during endocytosis for influenza A (IAV) and SARS coronaviruses. Drawing upon extensive literature from the last few decades and latest research, I analyze and compare the circumstances in which IAV and SARS-coronavirus can undertake endocytotic pathways that are pH-dependent. While there are similarities in the pH-regulated patterns leading to fusion, the mechanisms and pH activation differ. In terms of fusion activity, the measured activation pH values for IAV, across all subtypes and species, vary between approximately 5.0 to 6.0, while SARS-coronavirus necessitates a lower pH of 6.0 or less. The main difference between the pH-dependent endocytic pathways is that the SARS-coronavirus, unlike IAV, require the presence of specific pH-sensitive enzymes (cathepsin L) during endosomal transport. Conversely, the conformational changes in the IAV virus under acidic conditions in endosomes occur due to the specific envelope glycoprotein residues and envelope protein ion channels (viroporins) getting protonated by H+ ions. Despite extensive research over several decades, comprehending the pH-triggered conformational alterations of viruses still poses a significant challenge. The precise mechanisms of protonation mechanisms of certain during endosomal transport for both viruses remain incompletely understood. In absence of evidence, further research is needed.
正在肆虐的新型冠状病毒肺炎疫情和流感流行，重新唤起了人们对于了解这些具有高度传染性的包膜病毒如何应对其微环境物理化学性质变化的兴趣。通过了解病毒在胞吞作用过程中利用宿主细胞pH环境的机制和条件，我们不仅可以更好地理解它们如何应对pH调节的抗病毒疗法，还能了解pH诱导的细胞外环境变化。本综述详细解释了甲型流感病毒（IAV）和严重急性呼吸综合征冠状病毒在胞吞作用期间，在病毒解体之前和引发病毒解体的pH依赖性病毒结构变化。借鉴过去几十年的大量文献和最新研究，我分析并比较了IAV和严重急性呼吸综合征冠状病毒能够进行pH依赖性胞吞途径的情况。虽然在导致融合的pH调节模式上存在相似之处，但机制和pH激活有所不同。在融合活性方面，所有亚型和物种的IAV测得的激活pH值在大约5.0至6.0之间变化，而严重急性呼吸综合征冠状病毒则需要6.0或更低的较低pH值。pH依赖性胞吞途径之间的主要区别在于，与IAV不同，严重急性呼吸综合征冠状病毒在内体运输过程中需要特定的pH敏感酶（组织蛋白酶L）的存在。相反，IAV病毒在内体酸性条件下的构象变化是由于特定的包膜糖蛋白残基和包膜蛋白离子通道（病毒孔蛋白）被H+离子质子化所致。尽管经过几十年的广泛研究，但理解病毒的pH触发构象变化仍然是一项重大挑战。两种病毒在内体运输过程中某些物质的质子化机制的确切机制仍未完全了解。在缺乏证据的情况下，还需要进一步研究。
