Institute of Infection, Veterinary and Ecological Sciences, University of Liverpoolgrid.10025.36, Liverpool, United Kingdom.
NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom.
mSphere. 2022 Jun 29;7(3):e0091321. doi: 10.1128/msphere.00913-21. Epub 2022 May 2.
New variants of SARS-CoV-2 are continuing to emerge and dominate the global sequence landscapes. Several variants have been labeled variants of concern (VOCs) because they may have a transmission advantage, increased risk of morbidity and/or mortality, or immune evasion upon a background of prior infection or vaccination. Placing the VOCs in context with the underlying variability of SARS-CoV-2 is essential in understanding virus evolution and selection pressures. Dominant genome sequences and the population genetics of SARS-CoV-2 in nasopharyngeal swabs from hospitalized patients were characterized. Nonsynonymous changes at a minor variant level were identified. These populations were generally preserved when isolates were amplified in cell culture. To place the Alpha, Beta, Delta, and Omicron VOCs in context, their growth was compared to clinical isolates of different lineages from earlier in the pandemic. The data indicated that the growth in cell culture of the Beta variant was more than that of the other variants in Vero E6 cells but not in hACE2-A549 cells. Looking at each time point, Beta grew more than the other VOCs in hACE2-A549 cells at 24 to 48 h postinfection. At 72 h postinfection there was no difference in the growth of any of the variants in either cell line. Overall, this work suggested that exploring the biology of SARS-CoV-2 is complicated by population dynamics and that these need to be considered with new variants. In the context of variation seen in other coronaviruses, the variants currently observed for SARS-CoV-2 are very similar in terms of their clinical spectrum of disease. SARS-CoV-2 is the causative agent of COVID-19. The virus has spread across the planet, causing a global pandemic. In common with other coronaviruses, SARS-CoV-2 genomes can become quite diverse as a consequence of replicating inside cells. This has given rise to multiple variants from the original virus that infected humans. These variants may have different properties and in the context of a widespread vaccination program may render vaccines less effective. Our research confirms the degree of genetic diversity of SARS-CoV-2 in patients. By comparing the growth of previous variants to the pattern seen with four variants of concern (VOCs) (Alpha, Beta, Delta, and Omicron), we show that, at least in cells, Beta variant growth exceeds that of Alpha, Delta, and Omicron VOCs at 24 to 48 h in both Vero E6 and hACE2-A549 cells, but by 72 h postinfection, the amount of virus is not different from that of the other VOCs.
新的 SARS-CoV-2 变体继续出现并主导着全球序列景观。一些变体已被标记为关注变体 (VOCs)，因为它们可能具有传播优势、增加发病率和/或死亡率的风险，或者在先前感染或接种疫苗的背景下逃避免疫。将 VOCs 置于 SARS-CoV-2 潜在变异性的背景下对于理解病毒进化和选择压力至关重要。从住院患者的鼻咽拭子中表征 SARS-CoV-2 的主导基因组序列和种群遗传学。确定了次要变体水平的非同义变化。当在细胞培养中扩增分离物时，这些群体通常被保留下来。为了将 Alpha、Beta、Delta 和 Omicron VOCs 置于上下文中，将它们的生长与大流行早期不同谱系的临床分离物进行了比较。数据表明，Beta 变体在 Vero E6 细胞中的生长速度超过了其他变体，但在 hACE2-A549 细胞中则不然。从每个时间点来看，Beta 在 hACE2-A549 细胞中感染后 24 至 48 小时的生长速度超过了其他 VOCs。感染后 72 小时，任何变体在两种细胞系中的生长都没有差异。总的来说，这项工作表明，探索 SARS-CoV-2 的生物学受到种群动态的影响，需要考虑到这些动态。就其他冠状病毒中观察到的变异而言，目前观察到的 SARS-CoV-2 变体在疾病的临床谱方面非常相似。SARS-CoV-2 是 COVID-19 的病原体。该病毒已在全球范围内传播，导致全球大流行。与其他冠状病毒一样，SARS-CoV-2 基因组在细胞内复制时会变得非常多样化。这导致了从最初感染人类的病毒中出现了多种变体。这些变体可能具有不同的特性，并且在广泛的疫苗接种计划背景下，可能会使疫苗效果降低。我们的研究证实了 SARS-CoV-2 在患者中的遗传多样性程度。通过将以前变体的生长情况与四个关注变体 (VOCs)（Alpha、Beta、Delta 和 Omicron）的模式进行比较，我们表明，至少在细胞中，Beta 变体在感染后 24 至 48 小时，在 Vero E6 和 hACE2-A549 细胞中，其生长速度超过了 Alpha、Delta 和 Omicron VOCs，但到感染后 72 小时，病毒数量与其他 VOCs 没有差异。
