Evidence map›Paper›PMID 30866780›Full record

ArticleEmerging microbes & infections2019

Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection.

Matthijs R A Welkers, Hana A Pawestri, Judy M Fonville, Ondri D Sampurno, Maarten Pater, Melle Holwerda, Alvin X Han, Colin A Russell, Rienk E Jeeninga, Vivi Setiawaty and 2 more

Open access · goldAbstract read
In one paragraph

Article in Emerging microbes & infections, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.2field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
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  7. Evolution of a fuzzy ribonucleoprotein complex in viral assembly.bioRxiv : the preprint server for biology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 5 countries.

Matthijs R A Welkersa Department of Medical Microbiology , Academic Medical Center , Amsterdam , Netherlands.ORCID http://orcid.org/0000-0002-2982-0278
Hana A Pawestrib National Institute of Health Research and Development, Ministry of Health , Jakarta , Indonesia.
Judy M Fonvillea Department of Medical Microbiology , Academic Medical Center , Amsterdam , Netherlands.
Ondri D Sampurnob National Institute of Health Research and Development, Ministry of Health , Jakarta , Indonesia.
Maarten Patera Department of Medical Microbiology , Academic Medical Center , Amsterdam , Netherlands.
Melle Holwerdaa Department of Medical Microbiology , Academic Medical Center , Amsterdam , Netherlands.
Alvin X Hana Department of Medical Microbiology , Academic Medical Center , Amsterdam , Netherlands.ORCID http://orcid.org/0000-0001-6281-8498
Colin A Russella Department of Medical Microbiology , Academic Medical Center , Amsterdam , Netherlands.ORCID http://orcid.org/0000-0002-2113-162X
Rienk E Jeeningaa Department of Medical Microbiology , Academic Medical Center , Amsterdam , Netherlands.
Vivi Setiawatyb National Institute of Health Research and Development, Ministry of Health , Jakarta , Indonesia.ORCID http://orcid.org/0000-0002-1196-7909
Menno D de Jonga Department of Medical Microbiology , Academic Medical Center , Amsterdam , Netherlands.ORCID http://orcid.org/0000-0002-8380-4738
Dirk Egginka Department of Medical Microbiology , Academic Medical Center , Amsterdam , Netherlands.ORCID http://orcid.org/0000-0002-4248-6008
Amsterdam UMC Location University of Amsterdam · NLNational Institute of Health · AMAgency for Science, Technology and Research · SGUniversity of Cambridge · GB

Funding

Medical Research Council MR/K021885/1
6 · The paper itself

Abstract

The continuing pandemic threat posed by avian influenza A/H5N1 viruses calls for improved insights into their evolution during human infection. We performed whole genome deep sequencing of respiratory specimens from 44 H5N1-infected individuals from Indonesia and found substantial within-host viral diversity. At nearly 30% of genome positions multiple amino acids were observed within or across samples, including positions implicated in aerosol transmission between ferrets. Amino acid variants detected our cohort were often found more frequently in available H5N1 sequences of human than avian isolates. We additionally identified previously unreported amino acid variants and multiple variants that increased in proportion over time in available sequential samples. Given the importance of the polymerase complex for host adaptation, we tested 121 amino acid variants found in the PB2, PB1 and PA subunits for their effects on polymerase activity in human cells. We identified multiple single amino acid variants in all three polymerase subunits that substantially increase polymerase activity including some with effects comparable to that of the widely recognized adaption and virulence marker PB2-E627 K. These results indicate highly dynamic evolutionary processes during human H5N1 virus infection and the potential existence of previously undocumented adaptive pathways.

Indexed as

Amino Acid SubstitutionEvolution, MolecularHEK293 CellsHigh-Throughput Nucleotide SequencingHumansIndonesiaInfluenza A Virus, H5N1 SubtypeInfluenza, HumanProtein ConformationViral ProteinsWhole Genome SequencingViral ProteinsH5N1human adaptationInfluenzapolymerase complex

Identifiers

PMID30866780
PMCPMC6455201
OpenAlexW2914501355

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.