Literature detail

Fitness Inference from Short-Read Data: Within-Host Evolution of a Reassortant H5N1 Influenza Virus.

Christopher J R Illingworth¹

Affiliations 1 institutions

Department of Genetics, University of Cambridge, Cambridge, United Kingdom [email protected].

PMID 26243288 2015 Mol Biol Evol eng ppublish

Article

Publication summary

We present a method to infer the role of selection acting during the within-host evolution of the influenza virus from short-read genome sequence data. Linkage disequilibrium between loci is accounted for by treating short-read sequences as noisy multilocus emissions from an underlying model of haplotype evolution. A hierarchical model-selection procedure is used to infer the underlying fitness landscape of the virus insofar as that landscape is explored by the viral population. In a first application of our method, we analyze data from an evolutionary experiment describing the growth of a reassortant H5N1 virus in ferrets. Across two sets of replica experiments we infer multiple alleles to be under selection, including variants associated with receptor binding specificity, glycosylation, and with the increased transmissibility of the virus. We identify epistasis as an important component of the within-host fitness landscape, and show that adaptation can proceed through multiple genetic pathways.

fitness landscape influenza linkage disequilibrium selection within-host evolution Genetic Fitness Adaptation, Physiological Alleles Animals Biological Evolution Evolution, Molecular Ferrets Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza A Virus, H5N1 Subtype Influenza, Human Linkage Disequilibrium Models, Genetic

Structured evidence records

Evidence records

5 total

Genomic Evolution 1 records

Genomic Evolution Extraction confidence 0.90

Key finding

Short-read genomic sequence analysis of a reassortant H5N1 influenza virus during growth in ferrets identified multiple alleles under selection related to receptor binding, glycosylation, and transmissibility, indicating complex within-host evolutionary pathways.

Virus

Host

Location

Supporting text

We present a method to infer the role of selection acting during the within-host evolution of the influenza virus from short-read genome sequence data... In a first application of our method, we analyze data from an evolutionary experiment describing the growth of a reassortant H5N1 virus in ferrets. Across two sets of replica experiments we infer multiple alleles to be under selection, including variants associated with receptor binding specificity, glycosylation, and with the increased transmissibility of the virus.

Genes or proteins: Hemagglutinin Glycoproteins
Analysis methods: genome sequencing; model-selection procedure; within-host evolutionary analysis

Host Range Experiment 1 records

Host Range Experiment Extraction confidence 0.85

Key finding

A reassortant H5N1 influenza virus was experimentally grown in ferrets to study within-host evolution and identify alleles under selection related to receptor binding and transmissibility.

Virus

Host

Location

Supporting text

In a first application of our method, we analyze data from an evolutionary experiment describing the growth of a reassortant H5N1 virus in ferrets.

Method: evolutionary experiment; virus growth
Experimental system: in vivo animal experiment

Molecular Adaptation 1 records

Molecular Adaptation Extraction confidence 0.95

Key finding

Within-host evolution of a reassortant H5N1 influenza virus in ferrets revealed alleles under selection linked to receptor binding specificity, glycosylation, and increased transmissibility.

Virus

Host

Location

Supporting text

Across two sets of replica experiments we infer multiple alleles to be under selection, including variants associated with receptor binding specificity, glycosylation, and with the increased transmissibility of the virus.

Genes or proteins: Hemagglutinin Glycoproteins
Receptors: receptor binding specificity
Mechanism types: receptor_binding; transmission_fitness; glycosylation

Receptor Usage 1 records

Receptor Usage Extraction confidence 0.80

Key finding

Variants under selection in the reassortant H5N1 influenza virus included changes affecting receptor binding specificity, indicating receptor-mediated adaptation within ferrets.

Virus

Host

Location

Supporting text

Recombination Or Reassortment 1 records

Recombination Or Reassortment Extraction confidence 0.90

Key finding

The article reports experimental analysis of within-host evolution of a reassortant H5N1 influenza virus grown in ferrets, linking reassortment to viral adaptation related to receptor binding and transmissibility.

Virus

Host

Location

Supporting text

In a first application of our method, we analyze data from an evolutionary experiment describing the growth of a reassortant H5N1 virus in ferrets.

Event type: reassortment

Citation context

References

50 references

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Evidence overview

Evidence 5

Types 5

Virus 1

Host 1

Evidence types

Genomic Evolution 1 Host Range Experiment 1 Molecular Adaptation 1 Receptor Usage 1 Recombination Or Reassortment 1

Linked entities

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Publication metadata

Journal: Molecular biology and evolution
Volume / Issue / Pages: 32 / 11 / 3012-26
ISSN: 1537-1719
Journal country: United States
DOI: 10.1093/molbev/msv171