Isolation of SARS-CoV-2 strains carrying a nucleotide mutation, leading to a stop codon in the ORF 6 protein

Delbue, Serena; D’Alessandro, Sarah; Signorini, Lucia; Dolci, Maria; Pariani, Elena; Bianchi, Michele Leonardo; Fattori, S.; Modenese, Annalisa; Galli, Cristina; Eberini, Ivano; Ferrante, Pasquale

doi:10.1080/22221751.2021.1884003

Cited by 15 publications

(11 citation statements)

References 16 publications

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“…In fact, monthly variations of codon numbers show that any nucleotide may be mutated to any other nucleotide during transmission of the virus ( Table S3 , data within purple frame). These observations are consistent with presence of all twelve possible mutation patterns in evolution of SARS-CoV-2 genome [27] , [28] and formation of premature stop codons in coding regions of ORF6 and ORF8 [34] , [35] . Deletion and insertion are other patterns of nucleotide mutations occurring in SARS-CoV-2 genome [19] , [36] .…”

Section: Discussionsupporting

confidence: 87%

Human SARS-CoV-2 has evolved to increase U content and reduce genome size

Wang

Chen

Liu

et al. 2022

International Journal of Biological Macromolecules

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Infections caused by SARS-CoV-2 have brought great harm to human health. After transmission for over two years, SARS-CoV-2 has diverged greatly and formed dozens of different lineages. Understanding the trend of its genome evolution could help foresee difficulties in controlling transmission of the virus. In this study, we conducted an extensive monthly survey and in-depth analysis on variations of nucleotide, amino acid and codon numbers in 311,260 virus samples collected till January 2022. The results demonstrate that the evolution of SARS-CoV-2 is toward increasing U-content and reducing genome-size. C, G and A to U mutations have all contributed to this U-content increase. Mutations of C, G and A at codon position 1, 2 or 3 have no significant difference in most SARS-CoV-2 lineages. Current viruses are more cryptic and more efficient in replication, and are thus less virulent yet more infectious. Delta and Omicron variants have high mutability over other lineages, bringing new threat to human health. This trend of genome evolution may provide a clue for tracing the origin of SARS-CoV-2, because ancestral viruses should have lower U-content and probably bigger genome-size.

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Section: Discussionsupporting

confidence: 87%

Human SARS-CoV-2 has evolved to increase U content and reduce genome size

Wang

Chen

Liu

et al. 2022

International Journal of Biological Macromolecules

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“…ORF6 of both SARS-CoV and SARS-CoV-2 can block nuclear import of STAT [157]. Multiple SARS-CoV-2 isolates have been found with truncations in ORF6, including in a nosocomial cluster, suggesting the viruses are able to transmit, at least in a hospital setting [158–160]. Virus replication kinetics of the variants with ORF6 truncations are equivalent to that of closely related isolates with intact ORF6 (160).…”

Section: Sars-cov-2 Mutations Outside the Spike Glycoproteinmentioning

confidence: 99%

SARS-CoV-2 one year on: evidence for ongoing viral adaptation

Peacock

Penrice-Randal

Hiscox

et al. 2021

Journal of General Virology

143

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SARS-CoV-2 is thought to have originated in the human population from a zoonotic spillover event. Infection in humans results in a variety of outcomes ranging from asymptomatic cases to the disease COVID-19, which can have significant morbidity and mortality, with over two million confirmed deaths worldwide as of January 2021. Over a year into the pandemic, sequencing analysis has shown that variants of SARS-CoV-2 are being selected as the virus continues to circulate widely within the human population. The predominant drivers of genetic variation within SARS-CoV-2 are single nucleotide polymorphisms (SNPs) caused by polymerase error, potential host factor driven RNA modification, and insertion/deletions (indels) resulting from the discontinuous nature of viral RNA synthesis. While many mutations represent neutral ‘genetic drift’ or have quickly died out, a subset may be affecting viral traits such as transmissibility, pathogenicity, host range, and antigenicity of the virus. In this review, we summarise the current extent of genetic change in SARS-CoV-2, particularly recently emerging variants of concern, and consider the phenotypic consequences of this viral evolution that may impact the future trajectory of the pandemic.

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“…Isolation and growth curves of SARS-CoV-2 strains carrying nonsynonymous amino acid mutations were performed. A comparison was performed with the SARS-CoV-2 B.1 strain (EPI_ISL_584051) previously isolated in our laboratory [ 29 ]. No significant differences were observed between the four growth curves ( p value > 0.05) ( Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

Circulation of SARS-CoV-2 Variants among Children from November 2020 to January 2022 in Trieste (Italy)

et al. 2022

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Introduction: The ongoing coronavirus disease 19 (COVID-19) outbreak involves the pediatric population, but to date, few reports have investigated the circulation of variants among children. Material and Methods: In this retrospective study, non-hospitalized pediatric patients with SARS-CoV-2-positive nasopharyngeal swabs (NPS) were enrolled at the Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste (Italy), from November 2020 to January 2022. SARS-CoV-2 variants were identified by in vitro viral isolation, amplification, automatic sequencing of the receptor binding domain (RBD) of the SARS-CoV-2 spike coding gene, and subsequent next-generation sequencing. The growth curves of the isolated strains were defined in vitro by infecting Vero-E6 cells and quantifying the viral load in the supernatants up to 72 h post-infection by qRT–PCR. The neutralization activity of sera obtained from a COVID-19 vaccinated subject, recovered (2020) patient, vaccinated and recovered (2021) patient, and seronegative subject was assessed by microneutralization assay against the different variants. Results: In total, 32 SARS-CoV-2-positive children, 16 (50%) females, with a median age of 1.4 years (range: 1 day–13 years), were enrolled. The D614G amino acid substitution was detected in all isolated and amplified viral strains. Of the 32 isolates, 4 (12.5%) carried a nonsynonymous nucleotide mutation leading to the N439K (3/4), lineage B.1.258 (∆H69/∆V70), and S477N (1/4) substitution. In 7/32 (21.8%) isolates, amino acid substitutions allowed the identification of a delta variant, lineage B.1.617.2-AY.43, and in 1/32 (3.1%), the Omicron strain (B.1.1.529.BA1) was identified. The growth curves of the B.1, B.1.258 (∆H69/∆V70), B.1.617.2-AY.43, and B.1.1.529.BA1 variants did not show any significant differences. A reduction in the serum neutralizing activity against B.1.258 (∆H69/∆V70) only in a vaccinated subject (1.7-fold difference), against B.1.617.2-AY.43 in a vaccinated subject and in recovered patients (12.7 and ≥2.5-fold differences, respectively), and against B.1.1.529.BA1 variant (57.6- and 1.4-fold differences in vaccinated and in vaccinated and recovered patients) were observed compared to the B.1 variant. Conclusions: SARS-CoV-2 variants carrying the B.1.258 (∆H69/∆V70) and S477N substitutions were reported here in a pediatric population for the first time. Although the growth rates of the isolated strains (B.1.258, B.1.617.2-AY.43, B.1.1.529.BA1) did not differ from the B.1 variant, neutralizing activity of the sera from vaccinated subjects significantly decreased against these variants. Attention should be devoted to the pediatric population to prevent the spread of new SARS-CoV-2 variants in an unvaccinated and predominantly naive population.

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Isolation of SARS-CoV-2 strains carrying a nucleotide mutation, leading to a stop codon in the ORF 6 protein

Cited by 15 publications

References 16 publications

Human SARS-CoV-2 has evolved to increase U content and reduce genome size

Human SARS-CoV-2 has evolved to increase U content and reduce genome size

SARS-CoV-2 one year on: evidence for ongoing viral adaptation

Circulation of SARS-CoV-2 Variants among Children from November 2020 to January 2022 in Trieste (Italy)

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