Deep Sequencing of Influenza A Virus from a Human Challenge Study Reveals a Selective Bottleneck and Only Limited Intrahost Genetic Diversification

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2016 Oct 7

PMID 27707932

Citations 62

Authors

Ashley Sobel Leonard

Micah T McClain

Gavin J D Smith

David E Wentworth

Rebecca A Halpin

Xudong Lin

Amy Ransier

Timothy B Stockwell

Suman R Das

Anthony S Gilbert

Robert Lambkin-Williams

Geoffrey S Ginsburg

Christopher W Woods

Katia Koelle

Affiliations

Soon will be listed here.

Abstract

Importance: Influenza viruses circulating among humans are known to rapidly evolve over time. However, little is known about how influenza virus evolves across single transmission events and over the course of a single infection. To address these issues, we analyze influenza virus sequences from a human challenge experiment that initiated infection with a cell- and egg-passaged viral stock, which appeared to have adapted during its preparation. We find that the subjects' viral populations differ genetically from the viral stock, with subjects' viral populations having lower representation of the amino-acid-changing variants that arose during viral preparation. We also find that most of the viral evolution occurring over single infections is characterized by further decreases in the frequencies of these amino-acid-changing variants and that only limited intrahost genetic diversification through new mutations is apparent. Our findings indicate that influenza virus populations can undergo rapid genetic changes during acute human infections.

Citing Articles

Quantifying the impact of vaccination on transmission and diversity of influenza A variants in pigs.

Li C, Culhane M, Schroeder D, Cheeran M, Galina Pantoja L, Jansen M J Virol. 2024; 98(12):e0124524.

PMID: 39530665 PMC: 11651001. DOI: 10.1128/jvi.01245-24.

Influenza A virus within-host evolution and positive selection in a densely sampled household cohort over three seasons.

Bendall E, Zhu Y, Fitzsimmons W, Rolfes M, Mellis A, Halasa N Virus Evol. 2024; 10(1):veae084.

PMID: 39444487 PMC: 11498174. DOI: 10.1093/ve/veae084.

Influenza A virus within-host evolution and positive selection in a densely sampled household cohort over three seasons.

Bendall E, Zhu Y, Fitzsimmons W, Rolfes M, Mellis A, Halasa N bioRxiv. 2024; .

PMID: 39229225 PMC: 11370358. DOI: 10.1101/2024.08.15.608152.

Sequence-based detection of emerging antigenically novel influenza A viruses.

Forna A, Weedop K, Damodaran L, Hassell N, Kondor R, Bahl J Proc Biol Sci. 2024; 291(2028):20240790.

PMID: 39140324 PMC: 11323087. DOI: 10.1098/rspb.2024.0790.

Defining the balance between optimal immunity and immunopathology in influenza virus infection.

Nguyen T, Rowntree L, Chua B, Thwaites R, Kedzierska K Nat Rev Immunol. 2024; 24(10):720-735.

PMID: 38698083 DOI: 10.1038/s41577-024-01029-1.

References

Illingworth C . Fitness Inference from Short-Read Data: Within-Host Evolution of a Reassortant H5N1 Influenza Virus. Mol Biol Evol. 2015; 32(11):3012-26. PMC: 4651230. DOI: 10.1093/molbev/msv171. View

Dohm J, Lottaz C, Borodina T, Himmelbauer H . Substantial biases in ultra-short read data sets from high-throughput DNA sequencing. Nucleic Acids Res. 2008; 36(16):e105. PMC: 2532726. DOI: 10.1093/nar/gkn425. View

McCrone J, Lauring A . Measurements of Intrahost Viral Diversity Are Extremely Sensitive to Systematic Errors in Variant Calling. J Virol. 2016; 90(15):6884-95. PMC: 4944299. DOI: 10.1128/JVI.00667-16. View

Wilkinson T, Li C, Chui C, Huang A, Perkins M, Liebner J . Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med. 2012; 18(2):274-80. DOI: 10.1038/nm.2612. View

Hoelzer K, Murcia P, Baillie G, Wood J, Metzger S, Osterrieder N . Intrahost evolutionary dynamics of canine influenza virus in naive and partially immune dogs. J Virol. 2010; 84(10):5329-35. PMC: 2863817. DOI: 10.1128/JVI.02469-09. View

Murcia P, Baillie G, Stack J, Jervis C, Elton D, Mumford J . Evolution of equine influenza virus in vaccinated horses. J Virol. 2013; 87(8):4768-71. PMC: 3624384. DOI: 10.1128/JVI.03379-12. View

Moody M, Zhang R, Walter E, Woods C, Ginsburg G, McClain M . H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination. PLoS One. 2011; 6(10):e25797. PMC: 3198447. DOI: 10.1371/journal.pone.0025797. View

Tapparel C, Cordey S, Junier T, Farinelli L, van Belle S, Soccal P . Rhinovirus genome variation during chronic upper and lower respiratory tract infections. PLoS One. 2011; 6(6):e21163. PMC: 3119694. DOI: 10.1371/journal.pone.0021163. View

Yang , Bielawski . Statistical methods for detecting molecular adaptation. Trends Ecol Evol. 2000; 15(12):496-503. PMC: 7134603. DOI: 10.1016/s0169-5347(00)01994-7. View

10.

Ping J, Keleta L, Forbes N, Dankar S, Stecho W, Tyler S . Genomic and protein structural maps of adaptive evolution of human influenza A virus to increased virulence in the mouse. PLoS One. 2011; 6(6):e21740. PMC: 3128085. DOI: 10.1371/journal.pone.0021740. View

11.

Quail M, Smith M, Coupland P, Otto T, Harris S, Connor T . A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers. BMC Genomics. 2012; 13:341. PMC: 3431227. DOI: 10.1186/1471-2164-13-341. View

12.

Welkers M, Jonges M, Jeeninga R, Koopmans M, de Jong M . Improved detection of artifactual viral minority variants in high-throughput sequencing data. Front Microbiol. 2015; 5:804. PMC: 4302989. DOI: 10.3389/fmicb.2014.00804. View

13.

Grad Y, Newman R, Zody M, Yang X, Murphy R, Qu J . Within-host whole-genome deep sequencing and diversity analysis of human respiratory syncytial virus infection reveals dynamics of genomic diversity in the absence and presence of immune pressure. J Virol. 2014; 88(13):7286-93. PMC: 4054443. DOI: 10.1128/JVI.00038-14. View

14.

Chen Z, Zhou H, Jin H . The impact of key amino acid substitutions in the hemagglutinin of influenza A (H3N2) viruses on vaccine production and antibody response. Vaccine. 2010; 28(24):4079-85. DOI: 10.1016/j.vaccine.2010.03.078. View

15.

Koboldt D, Chen K, Wylie T, Larson D, McLellan M, Mardis E . VarScan: variant detection in massively parallel sequencing of individual and pooled samples. Bioinformatics. 2009; 25(17):2283-5. PMC: 2734323. DOI: 10.1093/bioinformatics/btp373. View

16.

Koboldt D, Zhang Q, Larson D, Shen D, McLellan M, Lin L . VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 2012; 22(3):568-76. PMC: 3290792. DOI: 10.1101/gr.129684.111. View

17.

Moncla L, Zhong G, Nelson C, Dinis J, Mutschler J, Hughes A . Selective Bottlenecks Shape Evolutionary Pathways Taken during Mammalian Adaptation of a 1918-like Avian Influenza Virus. Cell Host Microbe. 2016; 19(2):169-80. PMC: 4761429. DOI: 10.1016/j.chom.2016.01.011. View

18.

Nakowitsch S, Wolschek M, Morokutti A, Ruthsatz T, Krenn B, Ferko B . Mutations affecting the stability of the haemagglutinin molecule impair the immunogenicity of live attenuated H3N2 intranasal influenza vaccine candidates lacking NS1. Vaccine. 2011; 29(19):3517-24. DOI: 10.1016/j.vaccine.2011.02.100. View

19.

Wright C, Morelli M, Thebaud G, Knowles N, Herzyk P, Paton D . Beyond the consensus: dissecting within-host viral population diversity of foot-and-mouth disease virus by using next-generation genome sequencing. J Virol. 2010; 85(5):2266-75. PMC: 3067773. DOI: 10.1128/JVI.01396-10. View

20.

Stack J, Murcia P, Grenfell B, Wood J, Holmes E . Inferring the inter-host transmission of influenza A virus using patterns of intra-host genetic variation. Proc Biol Sci. 2012; 280(1750):20122173. PMC: 3574438. DOI: 10.1098/rspb.2012.2173. View