Consecutive deletions in a unique Uruguayan SARS-CoV-2 lineage evidence the genetic variability potential of accessory genes

Panzera, Yanina; Calleros, Lucía; Goñi, Natalia; Marandino, Ana; Techera, Claudia; Grecco, Sofía; Ramos, Natália; Frabasile, Sandra; Tomás, Gonzalo; Condon, Emma; Cortinas, Maria-Noel; Ramas, Viviana; Cóppola, Leticia; Sorhouet, Cecilia; Mogdasy, Cristina; Chiparelli, Héctor; Arbiza, Juan; Delfraro, Adriana; Pérez, Ruben

doi:10.1371/journal.pone.0263563

Cited by 8 publications

(9 citation statements)

References 38 publications

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“…Although highly variable in position and length, frameshift deletions that induce truncation of accessory protein 7a are not unique. There are numerous independent occurrences of such a mutation across both A and B lineages of SARS-CoV-2, including among VOCs [31][32][33][34][35][36][37][38] . Global genomic surveillance of SARS-CoV-2 has shown that mutations frequently occur at the downstream regions of ORF7a with such changes often leading to premature stop codons resulting in protein products with reduced functional activity.…”

Section: Discussionmentioning

confidence: 99%

Genomic epidemiology of Delta SARS-CoV-2 during transition from elimination to suppression in Aotearoa New Zealand

et al. 2022

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New Zealand’s COVID-19 elimination strategy heavily relied on the use of genomics to inform contact tracing, linking cases to the border and to clusters during community outbreaks. In August 2021, New Zealand entered its second nationwide lockdown after the detection of a single community case with no immediately apparent epidemiological link to the border. This incursion resulted in the largest outbreak seen in New Zealand caused by the Delta Variant of Concern. Here we generated 3806 high quality SARS-CoV-2 genomes from cases reported in New Zealand between 17 August and 1 December 2021, representing 43% of reported cases. We detected wide geographical spread coupled with undetected community transmission, characterised by the apparent extinction and reappearance of genomically linked clusters. We also identified the emergence, and near replacement, of genomes possessing a 10-nucleotide frameshift deletion that caused the likely truncation of accessory protein ORF7a. By early October, New Zealand moved from an elimination strategy to a suppression strategy and the role of genomics changed markedly from being used to track and trace, towards population-level surveillance.

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Section: Discussionmentioning

confidence: 99%

Genomic epidemiology of Delta SARS-CoV-2 during transition from elimination to suppression in Aotearoa New Zealand

et al. 2022

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“…SARS-CoV-2 has accumulated many variations since its emergence in late 2019 [ 21 ]. Nucleotide substitutions that produce amino acid replacements constitute the primary raw material for genetic variation; however, many insertions and deletions (indels) are likely to be critical elements in coronavirus macro- and microevolution [ 22 , 23 , 24 , 25 , 26 , 27 ]. Although most indels negatively affect viral fitness, a small number of them emerged and spread in viral populations, suggesting a positive effect on viral fitness and adaptive evolution [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Deletions across the SARS-CoV-2 Genome: Molecular Mechanisms and Putative Functional Consequences of Deletions in Accessory Genes

et al. 2023

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The analysis of deletions may reveal evolutionary trends and provide new insight into the surprising variability and rapidly spreading capability that SARS-CoV-2 has shown since its emergence. To understand the factors governing genomic stability, it is important to define the molecular mechanisms of deletions in the viral genome. In this work, we performed a statistical analysis of deletions. Specifically, we analyzed correlations between deletions in the SARS-CoV-2 genome and repetitive elements and documented a significant association of deletions with runs of identical (poly-) nucleotides and direct repeats. Our analyses of deletions in the accessory genes of SARS-CoV-2 suggested that there may be a hypervariability in ORF7A and ORF8 that is not associated with repetitive elements. Such recurrent search in a “sequence space” of accessory genes (that might be driven by natural selection) did not yet cause increased viability of the SARS-CoV-2 variants. However, deletions in the accessory genes may ultimately produce new variants that are more successful compared to the viral strains with the conventional architecture of the SARS-CoV-2 accessory genes.

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“…It is possible that single and large deletions in accessory genes may create changes in genome organization to cause more virus fitness. [30][31][32] We detected 30 and 15 consecutive deleted amino acids in Pts 7 and 9.…”

Section: Sars-cov-2 Genome Analysismentioning

confidence: 86%

SARS‐CoV‐2 intrahost evolution in immunocompromised patients in comparison with immunocompetent populations after treatment

Ahmadi

Zadheidar

Sadeghi

et al. 2023

Journal of Medical Virology

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Many evidence suggests that long‐lasting infection can develop with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). This occurrence has been widely described in immunocompromised individuals. In these patients, ineffective clearance of virus infection provides an opportunity for developing immune escape mutants. This study aimed to characterize SARS‐CoV‐2 intrahost evolution in five immunocompromised in comparison with five immunocompetent COVID‐19 patients during treatment. We performed next‐generation sequencing (NGS) on collected two oropharyngeal samples from immunocompromised and immunocompetent COVID‐19 patients before and after treatment. In this study, we detected alpha and delta variants of SARS‐CoV‐2. The most common substitutions in structural proteins in patients with alpha variant were S‐ΔY143‐144, A570D, D614G and D1118H, and N‐R203K and G204R, and in delta variant S‐T19R, G142D, E156G, 157‐158del, L452R, T478K, D614G, D950N and N‐D63G, R203M and D377Y were dominant. The common variations in nonstructural and accessory proteins including nsp3‐A488S, P1228L, nsp6‐T77A, nsp12‐P323L, G671S, nsp13‐P77L, NS3‐S26L, and NS7a‐T120I were detected. Also some infrequent substitutions were seen in immunocompromised and immunocompetent patients. After treatment, nsp12‐V166A was emerged as a remdesivir resistance and S‐L452M in a patient with common variable immunodeficiency. S‐E484Q was detected in a patient with acute lymphoma leukemia. This study showed the possibility of the genetic diversity and development of some new mutations in immunocompromised patients. Therefore, surveillance of these patients to characterize any new variants is necessary.

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Consecutive deletions in a unique Uruguayan SARS-CoV-2 lineage evidence the genetic variability potential of accessory genes

Cited by 8 publications

References 38 publications

Genomic epidemiology of Delta SARS-CoV-2 during transition from elimination to suppression in Aotearoa New Zealand

Genomic epidemiology of Delta SARS-CoV-2 during transition from elimination to suppression in Aotearoa New Zealand

Deletions across the SARS-CoV-2 Genome: Molecular Mechanisms and Putative Functional Consequences of Deletions in Accessory Genes

SARS‐CoV‐2 intrahost evolution in immunocompromised patients in comparison with immunocompetent populations after treatment

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