ORCID Profile
0000-0002-7089-7680
Current Organisation
University of Oxford
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Publisher: The Royal Society
Date: 16-11-2022
Abstract: The raw material for viral evolution is provided by intra-host mutations occurring during replication, transcription or post-transcription. Replication and transcription of Coronaviridae proceed through the synthesis of negative-sense ‘antigenomes’ acting as templates for positive-sense genomic and subgenomic RNA. Hence, mutations in the genomes of SARS-CoV-2 and other coronaviruses can occur during (and after) the synthesis of either negative-sense or positive-sense RNA, with potentially distinct patterns and consequences. We explored for the first time the mutational spectrum of SARS-CoV-2 (sub)genomic and anti(sub)genomic RNA. We use a high-quality deep sequencing dataset produced using a quantitative strand-aware sequencing method, controlled for artefacts and sequencing errors, and scrutinized for accurate detection of within-host ersity. The nucleotide differences between negative- and positive-sense strand consensus vary between patients and do not show dependence on age or sex. Similarities and differences in mutational patterns between within-host minor variants on the two RNA strands suggested strand-specific mutations or editing by host deaminases and oxidative damage. We observe generally neutral and slight negative selection on the negative strand, contrasting with purifying selection in ORF1a, ORF1b and S genes of the positive strand of the genome.
Publisher: Cold Spring Harbor Laboratory
Date: 02-12-2022
DOI: 10.1101/2022.12.02.518847
Abstract: In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burdens, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of s les, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. Analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated in iduals with no known prior infection, the average Ct value was 0.94 lower among Alpha variant infections, compared those with the predecessor strain, B.1.177. However, among vaccinated in iduals, it was 0.34 lower among Delta variant infections, compared to those with the Alpha variant. In addition, the average Ct value decreased by 0.20 for every 10 year age increment of the infected in idual. In summary, within-host viral burdens are associated with age, in addition to the interplay of vaccination status and viral variant.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 16-04-2021
Abstract: A year into the severe acute respiratory syndrome coronavirus 2 pandemic, we are experiencing waves of new variants emerging. Some of these variants have worrying functional implications, such as increased transmissibility or antibody treatment escape. Lythgoe et al. have undertaken in-depth sequencing of more than 1000 hospital patients' isolates to find out how the virus is mutating within in iduals. Overall, there seem to be consistent and reproducible patterns of within-host virus ersity. The authors observed only one or two variants in most s les, but a few carried many variants. Although the evidence indicates strong purifying selection, including in the spike protein responsible for viral entry, the authors also saw evidence for transmission clusters associated with households and other possible superspreader events. After transmission, most variants fizzled out, but occasionally some initiated ongoing transmission and wider dissemination. Science , this issue p. eabg0821
Publisher: Cold Spring Harbor Laboratory
Date: 28-05-2020
DOI: 10.1101/2020.05.28.118992
Abstract: Extensive global s ling and whole genome sequencing of the pandemic virus SARS-CoV-2 have enabled researchers to characterise its spread, and to identify mutations that may increase transmission or enable the virus to escape therapies or vaccines. Two important components of viral spread are how frequently variants arise within in iduals, and how likely they are to be transmitted. Here, we characterise the within-host ersity of SARS-CoV-2, and the extent to which genetic ersity is transmitted, by quantifying variant frequencies in 1390 clinical s les from the UK, many from in iduals in known epidemiological clusters. We show that SARS-CoV-2 infections are characterised by low levels of within-host ersity across the entire viral genome, with evidence of strong evolutionary constraint in Spike, a key target of vaccines and antibody-based therapies. Although within-host variants can be observed in multiple in iduals in the same phylogenetic or epidemiological cluster, highly infectious in iduals with high viral load carry only a limited repertoire of viral ersity. Most viral variants are either lost, or occasionally fixed, at the point of transmission, consistent with a narrow transmission bottleneck. These results suggest potential vaccine-escape mutations are likely to be rare in infectious in iduals. Nonetheless, we identified Spike variants present in multiple in iduals that may affect receptor binding or neutralisation by antibodies. Since the fitness advantage of escape mutations in highly-vaccinated populations is likely to be substantial, resulting in rapid spread if and when they do emerge, these findings underline the need for continued vigilance and monitoring.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Katrina Lythgoe.