Correction for Dinis et al., Deep Sequencing Reveals Potential Antigenic Variants at Low Frequencies in Influenza A Virus-Infected Humans

Dinis, Jorge M.; Florek, Kelsey; Fatola, Omolayo O.; Moncla, Louise H.; Mutschler, James; Charlier, Olivia K.; Belongia, Edward A.; Friedrich, Thomas C.

doi:10.1128/jvi.01041-16

Cited by 3 publications

(2 citation statements)

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“…We recently reported evidence showing that vaccine pressure works to select influenza variants genetically distant from vaccine strains and affects the dynamics of the epidemic variants for humans [13]. At the beginning of the previous study, the phylogenetic method did not segregate viruses isolated from vaccinated and unvaccinated patients, as indicated in the report [17]. One possible explanation for the vaccine pressure not being reflected in the phylogenetic tree is that viruses that are able to infect vaccinated persons will become epidemic, irrespective of vaccination status.…”

Section: Discussionmentioning

confidence: 92%

Differences in the Hemagglutinin Amino Acids of Japanese and US Influenza A/H3N2 Viral Isolates and their Relationship with Vaccine Strain Differences

Chong¹,

Ikematsu²

2017

J Vaccines Vaccin

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The effects of vaccination on the dynamics of influenza virus remain largely unknown. Different A/H3N2 vaccine strains were used in Japan and the United States (US) in the 2014-2015 season. To examine how different vaccine strains affect the selection of surviving variants, we compared hemagglutinin (HA) sequences in Japan with those in the US. A total of 85 A/H3N2 samples from 38 vaccinated and 47 unvaccinated Japanese patients (33 from the 2013-2014 and 52 from the 2014-2015 Japanese seasons) were isolated and genetically analyzed using a nextgeneration sequencer for comparison with 113 US isolates (30 from the 2013-2014 season and 83 from the 2014-2015 season) referenced from the GenBank database. HA1 amino acid (AA) differences between Japan and the US for the 2014-2015 vaccine strains were found at sites 128 (epitope B), 142 (A), 145 (A) and 198 (B). 145S and 198S in Japanese isolates, which matched with those of the 2014-2015 vaccine strain, significantly decreased between the two seasons, contrary to the full maintenance of US isolates (57.6% vs. 5.8% for 145S, P<0.0001; 100.0% vs. 75.0% for 198S, P=0.0012). The predominance of 128A and 142G was also lost in Japanese isolates, as observed while matching these AAs with those of the 2014-2015 vaccine strain (72.7% vs. 19.2% for 128A, P<0.0001; 75.8% vs. 15.4% for 142G, P<0.0001). Our data suggest that vaccine selection might be associated with the emergence of influenza variants genetically distant from vaccine strains.

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Section: Discussionmentioning

confidence: 92%

Differences in the Hemagglutinin Amino Acids of Japanese and US Influenza A/H3N2 Viral Isolates and their Relationship with Vaccine Strain Differences

Chong¹,

Ikematsu²

2017

J Vaccines Vaccin

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show abstract

“…Thus, distinguishing true sequence variation from technical and experimental noise is challenging. Typically, several ad hoc metrics are used to filter variants, such as applying frequency and coverage cutoffs to sequencing data; however, the frequency at which identified variants are considered valid can vary widely ( 20 - 26 ). Most studies using large sample cohorts, or performing analyses on publicly available data, generally use single replicate data, despite evidence suggesting that replicate sequencing may be essential for filtering false-positive minority variants ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

Optimized quantification of intra-host viral diversity in SARS-CoV-2 and influenza virus sequence data

Roder

Johnson

Knoll

et al. 2023

mBio

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High error rates of viral RNA-dependent RNA polymerases lead to diverse intra-host viral populations during infection. Errors made during replication that are not strongly deleterious to the virus can lead to the generation of minority variants. However, accurate detection of minority variants in viral sequence data is complicated by errors introduced during sample preparation and data analysis. We used synthetic RNA controls and simulated data to test seven variant-calling tools across a range of allele frequencies and simulated coverages. We show that choice of variant caller and use of replicate sequencing have the most significant impact on single-nucleotide variant (SNV) discovery and demonstrate how both allele frequency and coverage thresholds impact both false discovery and false-negative rates. When replicates are not available, using a combination of multiple callers with more stringent cutoffs is recommended. We use these parameters to find minority variants in sequencing data from SARS-CoV-2 clinical specimens and provide guidance for studies of intra-host viral diversity using either single replicate data or data from technical replicates. Our study provides a framework for rigorous assessment of technical factors that impact SNV identification in viral samples and establishes heuristics that will inform and improve future studies of intra-host variation, viral diversity, and viral evolution. IMPORTANCE When viruses replicate inside a host cell, the virus replication machinery makes mistakes. Over time, these mistakes create mutations that result in a diverse population of viruses inside the host. Mutations that are neither lethal to the virus nor strongly beneficial can lead to minority variants that are minor members of the virus population. However, preparing samples for sequencing can also introduce errors that resemble minority variants, resulting in the inclusion of false-positive data if not filtered correctly. In this study, we aimed to determine the best methods for identification and quantification of these minority variants by testing the performance of seven commonly used variant-calling tools. We used simulated and synthetic data to test their performance against a true set of variants and then used these studies to inform variant identification in data from SARS-CoV-2 clinical specimens. Together, analyses of our data provide extensive guidance for future studies of viral diversity and evolution.

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Stabilizing selection of seasonal influenza receptor binding in populations with partial immunity

Hay

Junus

Riley

et al. 2020

Preprint

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AbstractMutations that alter cellular receptor binding of influenza hemagglutinin (HA) have profound effects on immune escape. Despite its high mutation rate, it is not fully understood why human influenza HA displays limited antigenic diversity across circulating viruses. We applied phylogenetic analysis and phylodynamic modeling to understand the evolutionary and epidemiological effects of binding avidity adaptation in humans using net charge as a marker for receptor binding avidity. Using 686 human influenza A/H3N2 HA sequences, we found that HA net charge followed an age-specific pattern. Phylogenetic analysis suggested that many binding variants have reduced fitness. Next, we developed an individual-based disease dynamic model embedded with within-host receptor binding adaptation and immune escape in a population with varied partial immunity. The model showed that mean binding avidity was unable to adapt to values that maximized transmissibility due to competing selective forces between within- and between-host levels. Overall, we demonstrated stabilizing selection of virus binding in a population with increasing partial immunity. These findings have potential implications in understanding the evolutionary mechanisms that determine the intensity of seasonal influenza epidemics.

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Correction for Dinis et al., Deep Sequencing Reveals Potential Antigenic Variants at Low Frequencies in Influenza A Virus-Infected Humans

Cited by 3 publications

References 0 publications

Differences in the Hemagglutinin Amino Acids of Japanese and US Influenza A/H3N2 Viral Isolates and their Relationship with Vaccine Strain Differences

Differences in the Hemagglutinin Amino Acids of Japanese and US Influenza A/H3N2 Viral Isolates and their Relationship with Vaccine Strain Differences

Optimized quantification of intra-host viral diversity in SARS-CoV-2 and influenza virus sequence data

Stabilizing selection of seasonal influenza receptor binding in populations with partial immunity

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