Journal article
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 and Immunity, Vol.6(2), pp.27-49
2021
Abstract
Background: 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.
Methods: 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.
Conclusions: 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.
Details
- Title
- 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
- Authors/Creators
- S. Leary (Author/Creator)S. Gaudieri (Author/Creator)M.D. Parker (Author/Creator)A. Chopra (Author/Creator)I. James (Author/Creator)S. Pakala (Author/Creator)E. Alves (Author/Creator)M. John (Author/Creator)B.B. Lindsey (Author/Creator)A.J. Keeley (Author/Creator)S.L. Rowland-Jones (Author/Creator)M.S. Swanson (Author/Creator)D.A. Ostrov (Author/Creator)J.L. Bubenik (Author/Creator)S.R. Das (Author/Creator)J. Sidney (Author/Creator)A. Sette (Author/Creator)T.I. de Silva (Author/Creator)E. Phillips (Author/Creator)S. Mallal (Author/Creator)
- Publication Details
- Pathogens and Immunity, Vol.6(2), pp.27-49
- Publisher
- Case Western Reserve University. Division of Infectious Diseases
- Identifiers
- 991005540719007891
- Copyright
- © 2021 Pathogens and Immunity
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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