Inter-Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical Outcomes

<p dir="ltr">The diversity of RNA viruses dictates their evolution in a particular host, community or environment. Here, we reported within- and between-host pH1N1virus diversity at consensus and sub-consensus levels over a three-year period (2015–2017) and its implications on diseas...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Hebah A. Al Khatib (10494573) (author)
مؤلفون آخرون: Muna A. Al Maslamani (14777263) (author), Peter V. Coyle (6837260) (author), I. Richard Thompson (4278694) (author), Elmoubasher A. Farag (9913227) (author), Asmaa A. Al Thani (10494576) (author), Hadi M. Yassine (4675846) (author)
منشور في: 2020
الموضوعات:
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author Hebah A. Al Khatib (10494573)
author2 Muna A. Al Maslamani (14777263)
Peter V. Coyle (6837260)
I. Richard Thompson (4278694)
Elmoubasher A. Farag (9913227)
Asmaa A. Al Thani (10494576)
Hadi M. Yassine (4675846)
author2_role author
author
author
author
author
author
author_facet Hebah A. Al Khatib (10494573)
Muna A. Al Maslamani (14777263)
Peter V. Coyle (6837260)
I. Richard Thompson (4278694)
Elmoubasher A. Farag (9913227)
Asmaa A. Al Thani (10494576)
Hadi M. Yassine (4675846)
author_role author
dc.creator.none.fl_str_mv Hebah A. Al Khatib (10494573)
Muna A. Al Maslamani (14777263)
Peter V. Coyle (6837260)
I. Richard Thompson (4278694)
Elmoubasher A. Farag (9913227)
Asmaa A. Al Thani (10494576)
Hadi M. Yassine (4675846)
dc.date.none.fl_str_mv 2020-01-17T09:00:00Z
dc.identifier.none.fl_str_mv 10.3390/microorganisms8010133
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Inter-Versus_Intra-Host_Sequence_Diversity_of_pH1N1_and_Associated_Clinical_Outcomes/26232464
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Genetics
Biomedical and clinical sciences
Clinical sciences
Medical microbiology
deep sequencing technology
virus diversity
intra-host diversity
inter-host diversity
low-frequency variant
haplotype reconstruction
dc.title.none.fl_str_mv Inter-Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical Outcomes
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">The diversity of RNA viruses dictates their evolution in a particular host, community or environment. Here, we reported within- and between-host pH1N1virus diversity at consensus and sub-consensus levels over a three-year period (2015–2017) and its implications on disease severity. A total of 90 nasal samples positive for the pH1N1 virus were deep-sequenced and analyzed to detect low-frequency variants (LFVs) and haplotypes. Parallel evolution of LFVs was seen in the hemagglutinin (HA) gene across three scales: among patients (33%), across years (22%), and at global scale. Remarkably, investigating the emergence of LFVs at the consensus level demonstrated that within-host virus evolution recapitulates evolutionary dynamics seen at the global scale. Analysis of virus diversity at the HA haplotype level revealed the clustering of low-frequency haplotypes from early 2015 with dominant strains of 2016, indicating rapid haplotype evolution. Haplotype sharing was also noticed in all years, strongly suggesting haplotype transmission among patients infected during a specific influenza season. Finally, more than half of patients with severe symptoms harbored a larger number of haplotypes, mostly in patients under the age of five. Therefore, patient age, haplotype diversity, and the presence of certain LFVs should be considered when interpreting illness severity. In addition to its importance in understanding virus evolution, sub-consensus virus diversity together with whole genome sequencing is essential to explain variabilities in clinical outcomes that cannot be explained by either analysis alone.</p><h2>Other Information</h2><p dir="ltr">Published in: Microorganisms<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/microorganisms8010133" target="_blank">https://dx.doi.org/10.3390/microorganisms8010133</a></p>
eu_rights_str_mv openAccess
id Manara2_042c9489bf4d96b537baaed9b8648d28
identifier_str_mv 10.3390/microorganisms8010133
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/26232464
publishDate 2020
repository.mail.fl_str_mv
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rights_invalid_str_mv CC BY 4.0
spelling Inter-Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical OutcomesHebah A. Al Khatib (10494573)Muna A. Al Maslamani (14777263)Peter V. Coyle (6837260)I. Richard Thompson (4278694)Elmoubasher A. Farag (9913227)Asmaa A. Al Thani (10494576)Hadi M. Yassine (4675846)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesMedical microbiologydeep sequencing technologyvirus diversityintra-host diversityinter-host diversitylow-frequency varianthaplotype reconstruction<p dir="ltr">The diversity of RNA viruses dictates their evolution in a particular host, community or environment. Here, we reported within- and between-host pH1N1virus diversity at consensus and sub-consensus levels over a three-year period (2015–2017) and its implications on disease severity. A total of 90 nasal samples positive for the pH1N1 virus were deep-sequenced and analyzed to detect low-frequency variants (LFVs) and haplotypes. Parallel evolution of LFVs was seen in the hemagglutinin (HA) gene across three scales: among patients (33%), across years (22%), and at global scale. Remarkably, investigating the emergence of LFVs at the consensus level demonstrated that within-host virus evolution recapitulates evolutionary dynamics seen at the global scale. Analysis of virus diversity at the HA haplotype level revealed the clustering of low-frequency haplotypes from early 2015 with dominant strains of 2016, indicating rapid haplotype evolution. Haplotype sharing was also noticed in all years, strongly suggesting haplotype transmission among patients infected during a specific influenza season. Finally, more than half of patients with severe symptoms harbored a larger number of haplotypes, mostly in patients under the age of five. Therefore, patient age, haplotype diversity, and the presence of certain LFVs should be considered when interpreting illness severity. In addition to its importance in understanding virus evolution, sub-consensus virus diversity together with whole genome sequencing is essential to explain variabilities in clinical outcomes that cannot be explained by either analysis alone.</p><h2>Other Information</h2><p dir="ltr">Published in: Microorganisms<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/microorganisms8010133" target="_blank">https://dx.doi.org/10.3390/microorganisms8010133</a></p>2020-01-17T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/microorganisms8010133https://figshare.com/articles/journal_contribution/Inter-Versus_Intra-Host_Sequence_Diversity_of_pH1N1_and_Associated_Clinical_Outcomes/26232464CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/262324642020-01-17T09:00:00Z
spellingShingle Inter-Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical Outcomes
Hebah A. Al Khatib (10494573)
Biological sciences
Genetics
Biomedical and clinical sciences
Clinical sciences
Medical microbiology
deep sequencing technology
virus diversity
intra-host diversity
inter-host diversity
low-frequency variant
haplotype reconstruction
status_str publishedVersion
title Inter-Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical Outcomes
title_full Inter-Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical Outcomes
title_fullStr Inter-Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical Outcomes
title_full_unstemmed Inter-Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical Outcomes
title_short Inter-Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical Outcomes
title_sort Inter-Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical Outcomes
topic Biological sciences
Genetics
Biomedical and clinical sciences
Clinical sciences
Medical microbiology
deep sequencing technology
virus diversity
intra-host diversity
inter-host diversity
low-frequency variant
haplotype reconstruction