ArticleCold Spring Harbor molecular case studies2016
Analysis of intrapatient heterogeneity uncovers the microevolution of Middle East respiratory syndrome coronavirus.
Article in Cold Spring Harbor molecular case studies, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 53 citations in OpenAlex.
- Article
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- Quasispecies Nature of RNA Viruses: Lessons from the Past.Vaccines · 2023Review
- Molecular transition of SARS-CoV-2 from critical patients during the first year of the COVID-19 pandemic in Mexico City.Frontiers in cellular and infection microbiology · 2023Article
- SARS-CoV-2 quasi-species analysis from patients with persistent nasopharyngeal shedding.Scientific reports · 2022Article
- SARS-CoV-2 Mutant Spectra at Different Depth Levels Reveal an Overwhelming Abundance of Low Frequency Mutations.Pathogens (Basel, Switzerland) · 2022Article
- Vaccine breakthrough infections with SARS-CoV-2 Alpha mirror mutations in Delta Plus, Iota, and Omicron.The Journal of clinical investigation · 2022Article
- SARS-CoV-2 Point Mutation and Deletion Spectra and Their Association with Different Disease Outcomes.Microbiology spectrum · 2022Article
- Highlight of potential impact of new viral genotypes of SARS-CoV-2 on vaccines and anti-viral therapeutics.Gene reports · 2022Article
- Jumping a Moving Train: SARS-CoV-2 Evolution in Real Time.Journal of the Pediatric Infectious Diseases Society · 2021Review
- Quasispecies of SARS-CoV-2 revealed by single nucleotide polymorphisms (SNPs) analysis.Virulence · 2021Article
- Evidence of Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection After Recovery from Mild Coronavirus Disease 2019.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
- Catch Me if You Can: Superspreading of COVID-19.Trends in microbiology · 2021Review
- SARS-CoV-2 Quasispecies Provides an Advantage Mutation Pool for the Epidemic Variants.Microbiology spectrum · 2021Article
- Intrauterine vertical SARS-CoV-2 infection: a case confirming transplacental transmission followed by divergence of the viral genome.BJOG : an international journal of obstetrics and gynaecology · 2021Article
- Middle East respiratory syndrome coronavirus Spike protein variants exhibit geographic differences in virulence.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Genetic diversity through social heterosis can increase virulence in RNA viral infections and cancer progression.Royal Society open science · 2021Article
- Current Status of Putative Animal Sources of SARS-CoV-2 Infection in Humans: Wildlife, Domestic Animals and Pets.Microorganisms · 2021Review
- VERSO: A comprehensive framework for the inference of robust phylogenies and the quantification of intra-host genomic diversity of viral samples.Patterns (New York, N.Y.) · 2021Article
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Authors and funding
17 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Genome sequence analysis of Middle East respiratory syndrome coronavirus (MERS-CoV) variants from patient specimens has revealed the evolutionary dynamics and mechanisms of pathogenesis of the virus. However, most studies have analyzed the consensus sequences of MERS-CoVs, precluding an investigation of intrapatient heterogeneity. Here, we analyzed non-consensus sequences to characterize intrapatient heterogeneity in cases associated with the 2015 outbreak of MERS in South Korea. Deep-sequencing analysis of MERS-CoV genomes performed on specimens from eight patients revealed significant intrapatient variation; therefore, sequence heterogeneity was further analyzed using targeted deep sequencing. A total of 35 specimens from 24 patients (including a super-spreader) were sequenced to detect and analyze variants displaying intrapatient heterogeneity. Based on the analysis of non-consensus sequences, we demonstrated the intrapatient heterogeneity of MERS-CoVs, with the highest level in the super-spreader specimen. The heterogeneity could be transmitted in a close association with variation in the consensus sequences, suggesting the occurrence of multiple MERS-CoV infections. Analysis of intrapatient heterogeneity revealed a relationship between D510G and I529T mutations in the receptor-binding domain (RBD) of the viral spike glycoprotein. These two mutations have been reported to reduce the affinity of the RBD for human CD26. Notably, although the frequency of both D510G and I529T varied greatly among specimens, the combined frequency of the single mutants was consistently high (87.7% ± 1.9% on average). Concurrently, the frequency of occurrence of the wild type at the two positions was only 6.5% ± 1.7% on average, supporting the hypothesis that selection pressure exerted by the host immune response played a critical role in shaping genetic variants and their interaction in human MERS-CoVs during the outbreak.
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