| Autor: |
Shay Leary, Silvana Gaudieri, Matthew Parker, Abha Chopra, Ian James, Suman Pakala, Eric Alves, Mina John, Benjamin Lindsey, Alexander Keeley, Sarah Rowland-Jones, Maurice Swanson, David Ostrov, Jodi Bubenik, Suman Das, John Sidney, Alessandro Sette, COVID-19 Genomics UK (COG-UK) consortium, Thushan de Silva, Elizabeth Phillips, Simon Mallal |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Pathogens and Immunity, Vol 6, Iss 2 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2469-2964 |
| DOI: |
10.20411/pai.v6i2.460 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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