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AuthorAl Khatib, Hebah A.
AuthorAl Maslamani, , Muna A.
AuthorV. Coyle, Peter
AuthorThompson, I. Richard Thompson
AuthorA. Farag, Elmoubasher
AuthorAl Thani, Asmaa A.
AuthorM. Yassine, Hadi
Available date2020-09-06T07:44:32Z
Publication Date2020-01-08
Publication NameMicroorganisms
Identifierhttp://dx.doi.org/10.3390/microorganisms8010133
CitationAl Khatib, H.A.; Al Maslamani, M.A.; Coyle, P.V.; Thompson, I.R.; Farag, E.A.; Al Thani, A.A.; Yassine, H.M. Inter-Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical Outcomes. Microorganisms 2020, 8, 133.
URIhttp://hdl.handle.net/10576/15962
AbstractThe 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.
Languageen
PublisherMDPI
Subjectdeep sequencing technology
virus diversity
intra-host diversity
inter-host diversity
low-frequency
haplotype reconstruction.
TitleInter-Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical Outcomes
TypeArticle
dc.accessType Open Access


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