Acute SARS-CoV-2 infections harbor limited within-host diversity and transmit via tight transmission bottlenecks.
Acute SARS-CoV-2 infections harbor limited within-host diversity and transmit via tight transmission bottlenecks.
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DOI：
10.1371/journal.ppat.1009849
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发表时间：
2021-08
期刊：
影响因子：
6.7
通讯作者：
Moncla LH
中科院分区：
文献类型：
--
作者：
Braun KM;Moreno GK;Wagner C;Accola MA;Rehrauer WM;Baker DA;Koelle K;O'Connor DH;Bedford T;Friedrich TC;Moncla LH
不同的SARS-CoV-2谱系的出现引起了人们的担忧，即引起免疫逃逸或取代循环谱系的能力的新变种可能出现在个体宿主中。尽管越来越多的证据表明，在长期感染过程中会出现新的变异，但大多数感染都是急性的。因此，对于预测SARS-CoV-2长期进化的速度，了解变异株在急性感染的宿主中出现和传播的效率是至关重要的。为了表征宿主内多样性是如何产生和传播的，我们将广泛的实验室和生物信息学控制与宿主内和宿主间多样性的度量结合到133个SARS-CoV-2急性感染个体的基因组中。我们发现，宿主内的多样性很低，传播瓶颈很窄，发现大多数感染的病毒很少。宿主内变异很少传播，即使在同一个家庭中的个人之间也是如此，而且很少在更广泛的社区中检测到与系统发育相关的感染。这些发现表明，寄主内产生的大部分变异在传播过程中丢失。RNA病毒在受感染的个体宿主内产生多样性。这种遗传多样性可以用来追踪病毒在个体内感染过程中的演变过程，以及病毒在个体之间的传播。为了研究SARS-CoV-2多样性是如何产生和传播的，我们对从威斯康星州急性感染者分离的133个SARS-CoV-2基因组进行了深度测序。我们利用来自威斯康星州的一致基因组的大型数据集来调查变异是如何在周围社区内传播的，并使用一个独特的家庭数据集来估计在流行病学相关的个人之间传播的病毒的数量。我们发现，大多数SARS-CoV-2感染的特征是宿主内多样性有限，并且绝大多数宿主内单核苷酸变体(ISNV)在传播过程中丢失。我们没有发现变异经常沿着系统发育相关的感染传播的证据，并估计大多数感染是由极少数独特的病毒粒子建立的。有限的宿主内多样性和严格的传播瓶颈相结合，可能会减缓SARS-CoV-2未来进化的步伐，并表明宿主内广泛进化可能是罕见的。
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. RNA viruses generate diversity within individual, infected hosts. This genetic diversity can be used to trace how viruses evolve during the course of infection within individuals, and transmission between them. To investigate how SARS-CoV-2 diversity is generated and propagated, we deep sequenced 133 SARS-CoV-2 genomes isolated from acutely infected individuals in Wisconsin. We capitalize on a large dataset of consensus genomes from Wisconsin to investigate how variants are transmitted within the surrounding community, and use a unique household dataset to estimate the number of viruses that are transmitted between epidemiologically linked individuals. We find that most SARS-CoV-2 infections are characterized by limited within-host diversity, and that the vast majority of intra-host single nucleotide variants (iSNVs) are lost during transmission. We do not find evidence that variation is frequently propagated along phylogenetically linked infections, and estimate that most infections are founded by very few unique virions. The combination of limited within-host diversity and tight transmission bottlenecks may slow the pace of SARS-CoV-2 evolution in the future, and suggests that extensive within-host evolution is likely rare.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
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影响因子：
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作者：
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作者：
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作者：
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SARS-COV-2内部多样性和传播。
DOI：
10.1126/science.abg0821
发表时间：
2021-04-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lythgoe KA;Hall M;Ferretti L;de Cesare M;MacIntyre-Cockett G;Trebes A;Andersson M;Otecko N;Wise EL;Moore N;Lynch J;Kidd S;Cortes N;Mori M;Williams R;Vernet G;Justice A;Green A;Nicholls SM;Ansari MA;Abeler-Dörner L;Moore CE;Peto TEA;Eyre DW;Shaw R;Simmonds P;Buck D;Todd JA;Oxford Virus Sequencing Analysis Group (OVSG);Connor TR;Ashraf S;da Silva Filipe A;Shepherd J;Thomson EC;COVID-19 Genomics UK (COG-UK) Consortium;Bonsall D;Fraser C;Golubchik T
通讯作者：
Golubchik T