Generation of a Novel SARS-CoV-2 Sub-genomic RNA Due to the R203K/G204R Variant in Nucleocapsid: Homologous Recombination has Potential to Change SARS-CoV-2 at Both Protein and RNA Level.


Leary, Shay ORCID: 0000-0002-6966-2294, Gaudieri, Silvana, Parker, Matthew D, Chopra, Abha ORCID: 0000-0001-5008-9080, James, Ian, Pakala, Suman, Alves, Eric ORCID: 0000-0002-6072-708X, John, Mina, Lindsey, Benjamin B ORCID: 0000-0003-4227-2592, Keeley, Alexander J ORCID: 0000-0001-9386-1157 et al (show 11 more authors) (2021) Generation of a Novel SARS-CoV-2 Sub-genomic RNA Due to the R203K/G204R Variant in Nucleocapsid: Homologous Recombination has Potential to Change SARS-CoV-2 at Both Protein and RNA Level. Pathogens & immunity, 6 (2). pp. 27-49.

Access the full-text of this item by clicking on the Open Access link.

Abstract

<h4>Background</h4>Genetic variations across the SARS-CoV-2 genome may influence transmissibility of the virus and the host's anti-viral immune response, in turn affecting the frequency of variants over time. In this study, we examined the adjacent amino acid polymorphisms in the nucleocapsid (R203K/G204R) of SARS-CoV-2 that arose on the background of the spike D614G change and describe how strains harboring these changes became dominant circulating strains globally.<h4>Methods</h4>Deep-sequencing data of SARS-CoV-2 from public databases and from clinical samples were analyzed to identify and map genetic variants and sub-genomic RNA transcripts across the genome. Results: Sequence analysis suggests that the 3 adjacent nucleotide changes that result in the K203/R204 variant have arisen by homologous recombination from the core sequence of the leader transcription-regulating sequence (TRS) rather than by stepwise mutation. The resulting sequence changes generate a novel sub-genomic RNA transcript for the C-terminal dimerization domain of nucleocapsid. Deep-sequencing data from 981 clinical samples confirmed the presence of the novel TRS-CS-dimerization domain RNA in individuals with the K203/R204 variant. Quantification of sub-genomic RNA indicates that viruses with the K203/R204 variant may also have increased expression of sub-genomic RNA from other open reading frames.<h4>Conclusions</h4>The finding that homologous recombination from the TRS may have occurred since the introduction of SARS-CoV-2 in humans, resulting in both coding changes and novel sub-genomic RNA transcripts, suggests this as a mechanism for diversification and adaptation within its new host.

Item Type: Article
Uncontrolled Keywords: COVID-19 Genomics UK (COG-UK) consortium
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 09 May 2022 08:57
Last Modified: 18 Mar 2024 03:22
DOI: 10.20411/pai.v6i2.460
Open Access URL: https://www.paijournal.com/index.php/paijournal/ar...
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3154486
Dimensions
Altmetric
CORE (COnnecting REpositories)