Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
PLoS Pathog. 2021 Aug 23;17(8):e1009849. doi: 10.1371/journal.ppat.1009849. eCollection 2021 Aug.
The emergence of divergent SARS-CoV-2 lineages has raised concern that novel variants eliciting immune escape or the ability to displace circulating lineages could emerge within individual hosts. Though growing evidence suggests that novel variants arise during prolonged infections, most infections are acute. Understanding how efficiently variants emerge and transmit among acutely-infected hosts is therefore critical for predicting the pace of long-term SARS-CoV-2 evolution. To characterize how within-host diversity is generated and propagated, we combine extensive laboratory and bioinformatic controls with metrics of within- and between-host diversity to 133 SARS-CoV-2 genomes from acutely-infected individuals. We find that within-host diversity is low and transmission bottlenecks are narrow, with very few viruses founding most infections. Within-host variants are rarely transmitted, even among individuals within the same household, and are rarely detected along phylogenetically linked infections in the broader community. These findings suggest that most variation generated within-host is lost during transmission.
SARS-CoV-2 谱系的出现引发了人们的担忧，即可能会在个体宿主中出现逃避免疫或取代流行谱系的新型变异体。尽管越来越多的证据表明，新型变异体是在长时间感染过程中产生的，但大多数感染是急性的。因此，了解变异体在急性感染宿主中出现和传播的效率对于预测 SARS-CoV-2 长期进化的速度至关重要。为了描述宿主内多样性的产生和传播方式，我们将广泛的实验室和生物信息学控制与个体内和个体间多样性的度量标准相结合，对来自急性感染个体的 133 个 SARS-CoV-2 基因组进行了分析。我们发现，宿主内多样性很低，传播瓶颈很窄，只有极少数病毒引发了大多数感染。宿主内变异体很少传播，即使在同一家庭的个体之间也是如此，并且在更广泛的社区中与谱系相关的感染中很少检测到。这些发现表明，大多数在宿主内产生的变异体在传播过程中丢失。
