The Evolution and Biology of SARS-CoV-2 Variants
The Evolution and Biology of SARS-CoV-2 Variants
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DOI：
10.1101/cshperspect.a041390
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发表时间：
2022-05-01
影响因子：
5.4
通讯作者：
Robertson, David L.
中科院分区：
文献类型：
--
作者：
Telenti, Amalio;Hodcroft, Emma B.;Robertson, David L.
如果没有对这种新型人类冠状病毒的遗传学和进化的研究，我们对仍在发展的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行的了解将是极其有限的。自2019年底SARS-CoV-2进入人类群体以来，大规模的基因组测序工作已经提供了对SARS-CoV-2全球传播和多样化的近实时跟踪。这些数据支持了对它的起源、流行病学和对人类的适应性的分析：主要是免疫逃避和增加的传播性。尽管SARS-CoV-2是一种新的人类病原体，但它具有很强的人际传播能力。在其在人类中的快速传播过程中，SARS-CoV-2进化出了独立的新形式，即所谓的“关注变体”，这些变体更适合于人与人之间的传播。SARS-CoV-1和SARS-CoV-2的蝙蝠冠状病毒祖先对人类（和其他哺乳动物）感染的最重要适应是使用血管紧张素转换酶2（ACE 2）受体。放松的结构限制为SARS相关冠状病毒刺突蛋白提供了可塑性，使其能够适应抗原性结果的重要氨基酸替换，而不损害与ACE 2结合的能力。虽然大量的研究集中在病毒刺突蛋白作为抗原进化和传播性变化的主要决定因素上，但也有越来越多的证据表明病毒蛋白质组的其他区域对病毒-宿主相互作用的贡献。尽管目前重组体的群体传播水平较低，但当不同的变异体共同传播时，检测到SARS-CoV-2分支之间的重组，增加了出现具有新特性的病毒的风险。将计算和机器学习方法应用于基因组序列数据集，以生成实验可验证的预测，将作为新变异监测的预警系统，并将在未来的疫苗规划中发挥重要作用。Omicron是最新的SARS-CoV-2变异体，它将注意力集中在抗原性的阶跃变化事件，即“转变”，而不是增量“漂移”变化。Omicron的传播性增加和抗原转变都导致它容易在完全接种疫苗和/或先前感染的人中引起感染。Omicron的毒力，虽然相对于它所取代的变体Delta有所降低，但它在很大程度上取决于个体过去的免疫暴露，这是一个明确的信号，即加强疫苗接种可以防止严重疾病。目前，SARS-CoV-2已被证明是一种危险的新人类呼吸道病原体，具有不可预测的进化能力，导致未来变异的风险太大，无法确保世界所有地区都通过病毒基因组测序进行筛查，通过可用和负担得起的疫苗进行保护，并制定非惩罚性战略来检测和应对新的令人担忧的变异。
Our understanding of the still unfolding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic would have been extremely limited without the study of the genetics and evolution of this new human coronavirus. Large-scale genome-sequencing efforts have provided close to real-time tracking of the global spread and diversification of SARS-CoV-2 since its entry into the human population in late 2019. These data have underpinned analysis of its origins, epidemiology, and adaptations to the human population: principally immune evasion and increasing transmissibility. SARS-CoV-2, despite being a new human pathogen, was highly capable of human-to-human transmission. During its rapid spread in humans, SARS-CoV-2 has evolved independent new forms, the so-called "variants of concern," that are better optimized for human-to-human transmission. The most important adaptation of the bat coronavirus progenitor of both SARS-CoV-1 and SARS-CoV-2 for human infection (and other mammals) is the use of the angiotensin-converting enzyme 2 (ACE2) receptor. Relaxed structural constraints provide plasticity to SARS-related coronavirus spike protein permitting it to accommodate significant amino acid replacements of antigenic consequence without compromising the ability to bind to ACE2. Although the bulk of research has justifiably concentrated on the viral spike protein as the main determinant of antigenic evolution and changes in transmissibility, there is accumulating evidence for the contribution of other regions of the viral proteome to virus-host interaction. Whereas levels of community transmission of recombinants compromising genetically distinct variants are at present low, when divergent variants cocirculate, recombination between SARS-CoV-2 clades is being detected, increasing the risk that viruses with new properties emerge. Applying computational and machine learning methods to genome sequence data sets to generate experimentally verifiable predictions will serve as an early warning system for novel variant surveillance and will be important in future vaccine planning. Omicron, the latest SARS-CoV-2 variant of concern, has focused attention on step change antigenic events, "shift," as opposed to incremental "drift" changes in antigenicity. Both an increase in transmissibility and antigenic shift in Omicron led to it readily causing infections in the fully vaccinated and/or previously infected. Omicron's virulence, while reduced relative to the variant of concern it replaced, Delta, is very much premised on the past immune exposure of individuals with a clear signal that boosted vaccination protects from severe disease. Currently, SARS-CoV-2 has proven itself to be a dangerous new human respiratory pathogen with an unpredictable evolutionary capacity, leading to a risk of future variants too great not to ensure all regions of the world are screened by viral genome sequencing, protected through available and affordable vaccines, and have non-punitive strategies in place for detecting and responding to novel variants of concern.