Amino acid substitutions associated with treatment failure of hepatitis C virus infection

Soria, María Eugenia; García-Crespo, Carlos; Martínez-González, Brenda; Vázquez-Sirvent, Lucía; Lobo-Vega, Rebeca; Ávila, Ana Isabel de; Gallego, Isabel; Chen, Qian; García-Cehic, Damir; Llorens-Revull, Meritxell; Briones, Carlos; Gómez, Jordi; Ferrer-Orta, Cristina; Verdaguer, N.; Gregori, Josep; Rodríguez‐Frías, Francisco; Buti, María; Esteban, Juan Ignacio; Domingo, Esteban; Quer, Josep; Perales, Celia

doi:10.1101/2020.07.03.180240

Cited by 2 publications

(1 citation statement)

References 52 publications

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“…Ultra-Deep Sequencing of SARS-CoV-2 from Infected Patients. PCR products were adjusted to 4 x 10 9 molecules/μl before generating DNA pools that were purified using Kapa Pure Beads (Kapabiosystems, Roche), and quantified using Qubit as previously described (38)(39)(40), and then fixed at 1.5 ng/μl. Purified DNA pools were further processed using the DNA library preparation kit Kapa Hyper Prep kit (Roche), during which each pool was indexed using SeqCap Adapter Kit A/B (Nimblegen) (24 Index).…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 Point Mutation and Deletion Spectra, and Their Association with Different Disease Outcome

Martínez-González

Soria

Vázquez-Sirvent

et al. 2022

Preprint

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Mutant spectra of RNA viruses are important to understand viral pathogenesis, and response to selective pressures. There is a need to characterize the complexity of mutant spectra in coronaviruses sampled from infected patients. In particular, the possible relationship between SARS-CoV-2 mutant spectrum complexity and disease associations has not been established. In the present study, we report an ultra-deep sequencing (UDS) analysis of the mutant spectrum of amplicons from the nsp12 (polymerase)- and spike (S)-coding regions of thirty nasopharyngeal isolates (diagnostic samples) of SARS-CoV-2 of the first COVID-19 pandemic wave (Madrid, Spain, April 2020) classified according to the severity of ensuing COVID-19. Low frequency mutations and deletions, counted relative to the consensus sequence of the corresponding isolate, were overwhelmingly abundant. We show that the average number of different point mutations, mutations per haplotype and several diversity indices was significantly higher in SARS-CoV-2 isolated from patients who developed mild disease than in those associated with moderate or severe disease (exitus). No such bias was observed with RNA deletions. Location of amino acid substitutions in the three dimensional structures of nsp12 (polymerase) and S suggest significant structural or functional effects. Thus, patients who develop mild symptoms may be a richer source of genetic variants of SARS-CoV-2 than patients with moderate or severe COVID-19.

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Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 Point Mutation and Deletion Spectra, and Their Association with Different Disease Outcome

Martínez-González

Soria

Vázquez-Sirvent

et al. 2022

Preprint

Self Cite

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Dissimilar conservation pattern in hepatitis C virus mutant spectra, consensus sequences, and data banks

García-Crespo

Soria

Gallego

et al. 2020

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AbstractThe influence of quasispecies dynamics on long-term virus diversification in nature is a largely unexplored question. Specifically, whether intra-host nucleotide and amino acid variation in quasispecies fits variation observed in consensus sequences or data bank alignments is unknown. Genome conservation and dynamics simulations are used for the computational design of universal vaccines, therapeutic antibodies and pan-genomic antiviral agents. The expectation is that selection of escape mutants will be limited when mutations at conserved residues are required. This strategy assumes long-term (epidemiologically relevant) conservation but, critically, does not consider short-term (quasispecies-dictated) residue conservation. We have calculated mutant frequencies of individual loci from mutant spectra of hepatitis C virus (HCV) populations passaged in cell culture and from infected patients. Nucleotide or amino acid conservation in consensus sequences of the same populations, or in the Los Alamos HCV data bank did not match residue conservation in mutant spectra. The results relativize the concept of sequence conservation in viral genetics, and suggest that residue invariance in data banks is an insufficient basis for the design of universal viral ligands for clinical purposes. Our calculations suggest relaxed mutational restrictions during quasispecies dynamics, which may contribute to higher calculated short-term than long-term viral evolutionary rates.

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Amino acid substitutions associated with treatment failure of hepatitis C virus infection

Cited by 2 publications

References 52 publications

SARS-CoV-2 Point Mutation and Deletion Spectra, and Their Association with Different Disease Outcome

SARS-CoV-2 Point Mutation and Deletion Spectra, and Their Association with Different Disease Outcome

Dissimilar conservation pattern in hepatitis C virus mutant spectra, consensus sequences, and data banks

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