Evolution of viral quasispecies during SARS-CoV-2 infection

Jary, Aude; Leducq, Valentin; Malet, Isabelle; Marot, Stéphane; Klement-Frutos, Elise; Teyssou, Elisa; Soulié, Cathia; Abdi, Basma; Wirden, Marc; Pourcher, Valérie; Caumes, Éric; Cálvez, Vincent; Burrel, Sonia; Marcelin, Anne‐Geneviève; Boutolleau, David

doi:10.1016/j.cmi.2020.07.032

Cited by 112 publications

(120 citation statements)

References 16 publications

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“…Yet, no significant nucleotide differences (signature) were detected between URT and LRT variants in the S glycoprotein. Similar results have been reported with characterization of quasispecies differences between anatomical sites (URT vs. LRT), but also from one day to the next with sequential samples from a single patient, suggesting a complex dynamic distribution of variants ( 76 ). It has been recently reported that SARS-CoV-2 can be detected in multiple organs including pharynx, liver, pancreas, kidneys, heart and brain ( 77 , 78 ).…”

Section: Tissue-specific Patterns Of Sars-cov-2 Variantssupporting

confidence: 86%

New Insights Into the Physiopathology of COVID-19: SARS-CoV-2-Associated Gastrointestinal Illness

2021

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Although SARS-CoV-2 is considered a lung-tropic virus that infects the respiratory tract through binding to the ACE2 cell-surface molecules present on alveolar lungs epithelial cells, gastrointestinal symptoms have been frequently reported in COVID-19 patients. What can be considered an apparent paradox is that these symptoms (e.g., diarrhea), sometimes precede the development of respiratory tract illness as if the breathing apparatus was not its first target during viral dissemination. Recently, evidence was reported that the gut is an active site of replication for SARS-CoV-2. This replication mainly occurs in mature enterocytes expressing the ACE2 viral receptor and TMPRSS4 protease. In this review we question how SARS-CoV-2 can cause intestinal disturbances, whether there are pneumocyte-tropic, enterocyte-tropic and/or dual tropic strains of SARS-CoV-2. We examine two major models: first, that of a virus directly causing damage locally (e.g., by inducing apoptosis of infected enterocytes); secondly, that of indirect effect of the virus (e.g., by inducing changes in the composition of the gut microbiota followed by the induction of an inflammatory process), and suggest that both situations probably occur simultaneously in COVID-19 patients. We eventually discuss the consequences of the virus replication in brush border of intestine on long-distance damages affecting other tissues/organs, particularly lungs.

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Section: Tissue-specific Patterns Of Sars-cov-2 Variantssupporting

confidence: 86%

New Insights Into the Physiopathology of COVID-19: SARS-CoV-2-Associated Gastrointestinal Illness

2021

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“…For each patient, the patterns of variants in URT and LRT were profoundly different, indicating compartmentalized virus replication, as previously described [12]. However, no clear variant signature for each respiratory compartment was observed, and no significant difference of LRT and URT nucleotide diversity was observed.…”

Section: Discussionsupporting

confidence: 72%

Compartmentalized Replication of SARS-Cov-2 in Upper vs. Lower Respiratory Tract Assessed by Whole Genome Quasispecies Analysis

et al. 2020

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We report whole-genome and intra-host variability of SARS-Cov-2 assessed by next generation sequencing (NGS) in upper (URT) and lower respiratory tract (LRT) from COVID-19 patients. The aim was to identify possible tissue-specific patterns and signatures of variant selection for each respiratory compartment. Six patients, admitted to the Intensive Care Unit, were included in the study. Thirteen URT and LRT were analyzed by NGS amplicon-based approach on Ion Torrent Platform. Bioinformatic analysis was performed using both realized in-house and supplied by ThermoFisher programs. Phylogenesis showed clade V clustering of the first patients diagnosed in Italy, and clade G for later strains. The presence of quasispecies was observed, with variants uniformly distributed along the genome and frequency of minority variants spanning from 1% to ~30%. For each patient, the patterns of variants in URT and LRT were profoundly different, indicating compartmentalized virus replication. No clear variant signature and no significant difference in nucleotide diversity between LRT and URT were observed. SARS-CoV-2 presents genetic heterogeneity and quasispecies compartmentalization in URT and LRT. Intra-patient diversity was low. The pattern of minority variants was highly heterogeneous and no specific district signature could be identified, nevertheless, analysis of samples, longitudinally collected in patients, supported quasispecies evolution.

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“…Therefore, structural variations of SARS-CoV-2 often lead to alternative sgRNA transcripts and significant alterations in their translation products. These variants potentially exist as quasispecies to facilitate evolutionary selection and host adaptation as observed in other RNA viral species [34][35][36][37] .…”

Section: Full-length Iso-seq Analysis Revealed Extensive Structural Vmentioning

confidence: 99%

Subgenomic RNAs as molecular indicators of asymptomatic SARS-CoV-2 infection

Wong

Ngan

Goldfeder

et al. 2021

Preprint

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In coronaviridae such as SARS-CoV-2, subgenomic RNAs (sgRNA) are replicative intermediates, therefore, their abundance and structures could infer viral replication activity and severity of host infection. Here, we systematically characterized the sgRNA expression and their structural variation in 81 clinical specimens collected from symptomatic and asymptomatic individuals with a goal of assessing viral genomic signatures of disease severity. We demonstrated the highly coordinated and consistent expression of sgRNAs from individuals with robust infections that results in symptoms, and found their expression is significantly repressed in the asymptomatic infections, indicating that the ratio of sgRNAs to genomic RNA (sgRNA/gRNA) is highly correlated with the severity of the disease. Using long read sequencing technologies to characterize full-length sgRNA structures, we also observed widespread deletions in viral RNAs, and identified unique sets of deletions preferentially found primarily in symptomatic individuals, with many likely to confer changes in SARS-CoV-2 virulence and host responses. Furthermore, based on the sgRNA structures, the frequently occurred structural variants in SARS-CoV-2 genomes serves as a mechanism to further induce SARS-CoV-2 proteome complexity. Taken together, our results show that differential sgRNA expression and structural mutational burden both appear to be correlated with the clinical severity of SARS-CoV-2 infection. Longitudinally monitoring sgRNA expression and structural diversity could further guide treatment responses, testing strategies, and vaccine development.

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Evolution of viral quasispecies during SARS-CoV-2 infection

Cited by 112 publications

References 16 publications

New Insights Into the Physiopathology of COVID-19: SARS-CoV-2-Associated Gastrointestinal Illness

New Insights Into the Physiopathology of COVID-19: SARS-CoV-2-Associated Gastrointestinal Illness

Compartmentalized Replication of SARS-Cov-2 in Upper vs. Lower Respiratory Tract Assessed by Whole Genome Quasispecies Analysis

Subgenomic RNAs as molecular indicators of asymptomatic SARS-CoV-2 infection

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