Mutational signatures and heterogeneous host response revealed via large-scale characterization of SARS-CoV-2 genomic diversity

Graudenzi, Alex; Maspero, Davide; Angaroni, Fabrizio; Piazza, Rocco; Ramazzotti, Daniele

doi:10.1016/j.isci.2021.102116

Cited by 68 publications

(99 citation statements)

References 68 publications

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“…Despite the two studies having used different approaches for creating representative datasets of independent mutation events in a large collection of SARS-CoV-2 genomes, the main categories of mutation preferences APOBEC-like, ADAR-like, CpG-like and apparent ROS induced mutations were similar. Overall similar conclusions about prevailing mutagenic sources and signatures were in works addressing intra-host variations of SARS-CoV-2 [154,155]. In summary, resequencing of RNA virus genomes suggested major mutational processes generating diversity that can lead to development of new virus forms.…”

Section: Base Substitution Mutagenesis In Rna Virusessupporting

confidence: 62%

“…The sequence of a natural individual viral isolate is usually generated from a reference-based or de novo alignment of multiple small Illumina reads, thus it does not reflect the variations of individual viral RNAs but instead is an average of the total population [156]. However, the recent combination of deep Illumina sequencing, and advanced bioinformatics, allows intra-host variations to be addressed in genomes of a single viral species during an acute infection period [154,155,157,158], so some interhost variation can be revealed. Further, a combination of bioinformatics with metagenomics focusing on a small conserved element of RNA viruses, such as RdRp, made it possible to identify and interrogate the content of multispecies virome [66,159].…”

Section: Single-molecule Sequencing Applied To Rna Virome In the Environment And In Single Organismsmentioning

confidence: 99%

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From RNA World to SARS-CoV-2: The Edited Story of RNA Viral Evolution

Kockler

Gordenin

2021

Preprint

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The current SARS- CoV-2 pandemic underscores the importance of understanding the evolution of RNA genomes. While RNA is subject to the formation of similar lesions as DNA, the evolutionary and physiological impacts RNA lesions have on viral genomes are yet to be characterized. Lesions that may drive the evolution of RNA genomes can induce breaks that are repaired by recombination or can cause base substitution mutagenesis, also known as base editing. Over the past decade or so, base editing mutagenesis of DNA genomes has been subject to many studies, revealing that exposure of ssDNA is subject to hypermutation that is involved in the etiology of cancer. However, base editing of RNA genomes has not been studied to the same extent. Recently hypermutation of single-stranded RNA viral genomes have also been documented though its role in evolution and population dynamics. Here, we will summarize the current knowledge of key mechanisms and causes of RNA genome instability covering areas from the RNA world theory to the SARS- CoV-2 pandemic of today. We will also highlight the key questions that remain as it pertains to RNA genome instability, mutations accumulation, and experimental strategies for addressing these questions.

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Section: Base Substitution Mutagenesis In Rna Virusessupporting

confidence: 62%

Section: Single-molecule Sequencing Applied To Rna Virome In the Environment And In Single Organismsmentioning

confidence: 99%

From RNA World to SARS-CoV-2: The Edited Story of RNA Viral Evolution

Kockler

Gordenin

2021

Preprint

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“…Meanwhile, the fourth case (20–19731) is a "G" type, according to nucleotide substitutions in the positions 28 144 and 23 403 11 Everett [ 30 ] Research article USA COIVD-19 patients D614G, RNA-dependent RNA polymerase (RdRp) located on ORF1b The D614G substitution has been proposed to promote infection of human cells, and this variant has spread globally at the expense of other genotypes 12 Forni [ 31 ] Original article Italy SARS-CoV-2 genomes D614G Recent studies have indicated that the D614G variant, which is now prevalent worldwide, enhances viral infectivity 13 Forster [ 32 ] Research article Germany COVID-19 patients Three central variants: A variant B variant C variant Node B is derived from A by two mutations: the synonymous mutation T8782C and the non-synonymous mutation C28144T changing a leucine to a serine. Type C differs from its parent type B by the non-synonymous mutation G26144T, which changes a glycine to a valine 14 Gómez-Carballa [ 33 ] Research article Spain SARS-CoV-2 genomes C8782T, C18060T, T28144C, C29095T Sub-haplogroup A2 most likely originated in Europe from an Asian ancestor and gave rise to sub-clade A2a, which represents the major non-Asian outbreak, especially in Africa and Europe 15 Goren [ 34 ] Letter to the editor USA COIVD-19 patients TMPRSS2 Both SARS-CoV-2 and influenza are dependent on TMPRSS2 for infectivity, it is likely that SARS-CoV-2 will have a similar seasonal cycle; thus, the fall and winter are likely to see an increase in COVID-19 cases 16 Graudenzi [ 35 ] Research article Italy …”

Section: Resultsmentioning

confidence: 99%

Characterization of SARS-CoV-2 different variants and related morbidity and mortality: a systematic review

et al. 2021

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Introduction Coronavirus Disease-2019 (SARS-CoV-2) started its devastating trajectory into a global pandemic in Wuhan, China, in December 2019. Ever since, several variants of SARS-CoV-2 have been identified. In the present review, we aimed to characterize the different variants of SARS-CoV-2 and explore the related morbidity and mortality. Methods A systematic review including the current evidence related to different variants of SARS-CoV-2 and the related morbidity and mortality was conducted through a systematic search utilizing the keywords in the online databases including Scopus, PubMed, Web of Science, and Science Direct; we retrieved all related papers and reports published in English from December 2019 to September 2020. Results A review of identified articles has shown three main genomic variants, including type A, type B, and type C. we also identified three clades including S, V, and G. Studies have demonstrated that the C14408T and A23403G alterations in the Nsp12 and S proteins are the most prominent alterations in the world, leading to life-threatening mutations.The spike D614G amino acid change has become the most common variant since December 2019. From missense mutations found from Gujarat SARS-CoV-2 genomes, C28854T, deleterious mutation in the nucleocapsid (N) gene was significantly associated with patients' mortality. The other significant deleterious variant (G25563T) is found in patients located in Orf3a and has a potential role in viral pathogenesis. Conclusion Overall, researchers identified several SARS-CoV-2 variants changing clinical manifestations and increasing the transmissibility, morbidity, and mortality of COVID-19. This should be considered in current practice and interventions to combat the pandemic and prevent related morbidity and mortality.

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“…The recent emergence of mutational variants of SARS-CoV-2 (nCoV) around the globe suggests adaptive evolution of the virus, potentially affecting its transmissibility, infectivity, virulence and/or immune escape [1–4]. The primary target of current vaccines and monoclonal antibodies is the Spike protein which mediates viral attachment to and entry into host cells [5, 6].…”

Section: Introductionmentioning

confidence: 99%

Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants

Tchesnokova

Kulakesara

Larson

et al. 2021

Preprint

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The recent rise in mutational variants of SARS-CoV-2, especially with changes in the Spike protein, is of significant concern due to the potential ability for these mutations to increase viral infectivity, virulence and/or ability to escape protective antibodies. Here, we investigated genetic variations in a 414-583 amino acid region of the Spike protein, partially encompassing the ACE2 receptor-binding domain (RBD), across a subset of 570 nasopharyngeal samples isolated between April 2020 and February 2021, from Washington, California, Arizona, Colorado, Minnesota and Illinois. We found that samples isolated since November have an increased number of amino acid mutations in the region, with L452R being the dominant mutation. This mutation is associated with a recently discovered CAL.20C viral variant from clade 20C, lineage B.1.429, that since November-December 2020 is associated with multiple outbreaks and is undergoing massive expansion across California. In some samples, however, we found a distinct L452R-carrying variant of the virus that, upon detailed analysis of the GISAID database genomes, is also circulating primarily in California, but emerged even more recently. The newly identified variant derives from the clade 20A (lineage B.1.232) and is named CAL.20A. We also found that the SARS-CoV-2 strain that caused the only recorded case of infection in an ape - gorillas in the San Diego Zoo, reported in January 2021 - is CAL.20A. In contrast to CAL.20C that carries two additional to L452R mutations in the Spike protein, L452R is the only mutation found in CAL.20A. According to the phylogenetic analysis, however, emergence of CAL.20C was also specifically triggered by acquisition of the L452R mutation. Further analysis of GISAID-deposited genomes revealed that several independent L452R-carrying lineages have recently emerged across the globe, with over 90% of the isolates reported between December 2020 -February 2021. Taken together, these results indicate that the L452R mutation alone is of significant adaptive value to SARS-CoV-2 and, apparently, the positive selection for this mutation became particularly strong only recently, possibly reflecting viral adaptation to the containment measures or increasing population immunity. While the functional impact of L452R has not yet been extensively evaluated, leucine-452 is positioned in the receptor-binding motif of RBD, in the interface of direct contact with the ACE2 receptor. Its replacement with arginine is predicted to result in both a much stronger binding to the receptor and escape from neutralizing antibodies. If true, this in turn might lead to significantly increased infectivity of the L452R variants, warranting their close surveillance and in-depth functional studies.

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Mutational signatures and heterogeneous host response revealed via large-scale characterization of SARS-CoV-2 genomic diversity

Cited by 68 publications

References 68 publications

From RNA World to SARS-CoV-2: The Edited Story of RNA Viral Evolution

From RNA World to SARS-CoV-2: The Edited Story of RNA Viral Evolution

Characterization of SARS-CoV-2 different variants and related morbidity and mortality: a systematic review

Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants

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