Your browser doesn't support javascript.
The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection.
Goldswain, Hannah; Dong, Xiaofeng; Penrice-Randal, Rebekah; Alruwaili, Muhannad; Shawli, Ghada T; Prince, Tessa; Williamson, Maia Kavanagh; Raghwani, Jayna; Randle, Nadine; Jones, Benjamin; Donovan-Banfield, I'ah; Salguero, Francisco J; Tree, Julia A; Hall, Yper; Hartley, Catherine; Erdmann, Maximilian; Bazire, James; Jearanaiwitayakul, Tuksin; Semple, Malcolm G; Openshaw, Peter J M; Baillie, J Kenneth; Emmett, Stevan R; Digard, Paul; Matthews, David A; Turtle, Lance; Darby, Alistair C; Davidson, Andrew D; Carroll, Miles W; Hiscox, Julian A.
  • Goldswain H; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • Dong X; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • Penrice-Randal R; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • Alruwaili M; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • Shawli GT; Medical Laboratory Technology Department, Northern Border University, Arar City, Saudi Arabia.
  • Prince T; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • Williamson MK; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • Raghwani J; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
  • Randle N; Department of Zoology, University of Oxford, Oxford, UK.
  • Jones B; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • Donovan-Banfield I; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • Salguero FJ; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • Tree JA; NIHR Health Protection Unit in Emerging and Zoonotic Infections, Liverpool, UK.
  • Hall Y; UK Health Security Agency, Salisbury, UK.
  • Hartley C; UK Health Security Agency, Salisbury, UK.
  • Erdmann M; UK Health Security Agency, Salisbury, UK.
  • Bazire J; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • Jearanaiwitayakul T; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
  • Semple MG; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
  • Openshaw PJM; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
  • Baillie JK; Department of Microbiology, Mahidol University, Salaya, Thailand.
  • Emmett SR; NIHR Health Protection Unit in Emerging and Zoonotic Infections, Liverpool, UK.
  • Digard P; Department of Respiratory Medicine, Alder Hey Children's Hospital, Liverpool, UK.
  • Matthews DA; National Heart and Lung Institute, Imperial College London, London, UK.
  • Turtle L; The Roslin Institute, University of Edinburgh, Edinburgh, UK.
  • Davidson AD; Royal United Hospitals Bath NHS Foundation Trust, Bath, UK.
  • Carroll MW; Bristol Medical School, University of Bristol, Bristol, UK.
  • Hiscox JA; The Roslin Institute, University of Edinburgh, Edinburgh, UK.
Genome Biol ; 24(1): 47, 2023 03 13.
Article in English | MEDLINE | ID: covidwho-2260859
ABSTRACT

BACKGROUND:

The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure.

RESULTS:

Investigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant viral genome sequence. This is investigated in vivo and in vitro using SARS-CoV-2 with P323 and D614 in the dominant genome sequence and L323 and G614 in the minor variant population. During infection, there is rapid selection of L323 into the dominant viral genome sequence but not G614. Reverse genetics is used to create two viruses (either P323 or L323) with the same genetic background. L323 shows greater abundance of viral RNA and proteins and a smaller plaque morphology than P323.

CONCLUSIONS:

These data suggest that P323L is an important contribution in the emergence of variants with transmission advantages. Sequence analysis of viral populations suggests it may be possible to predict the emergence of a new variant based on tracking the frequency of minor variant genomes. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Genome Biol Journal subject: Molecular Biology / Genetics Year: 2023 Document Type: Article Affiliation country: S13059-023-02881-5

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Genome Biol Journal subject: Molecular Biology / Genetics Year: 2023 Document Type: Article Affiliation country: S13059-023-02881-5