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dc.contributor.authorNabakooza, Grace
dc.contributor.authorPastusiak, Andrzej
dc.contributor.authorKateete, David Patrick
dc.contributor.authorLutwama, Julius Julian
dc.contributor.authorKitayimbwa, John Mulindwa
dc.contributor.authorFrost, Simon David William
dc.date.accessioned2022-04-21T23:30:36Z
dc.date.available2022-04-21T23:30:36Z
dc.date.issued2022
dc.identifier.issn2057-1577
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336347
dc.description.abstractInfluenza type-A viruses (IAVs) present a global burden of human respiratory infections and mortality. Genome reassortment is an important mechanism through which epidemiologically novel influenza viruses emerge and a core step in the safe reassortment-incompetent live-attenuated influenza vaccine development. Currently, there are no data on the rate, spatial and temporal distribution, and role of reassortment in the evolution and diversification of IAVs circulating in Africa. We aimed to detect intra-subtype reassortment among Africa pandemic H1N1pdm09 (2009-10), seasonal H1N1pdm09 (2011-20), and seasonal H3N2 viruses and characterize the genomic architecture and temporal and spatial distribution patterns of the resulting reassortants. Our study was nested within the Uganda National Influenza Surveillance Programme. Next-generation sequencing was used to generate whole genomes (WGs) from 234 H1N1pdm09 (n = 116) and H3N2 (n = 118) viruses sampled between 2010 and 2018 from seven districts in Uganda. We combined our newly generated WGs with 658 H1N1pdm09 and 1131 H3N2 WGs sampled between 1994 and 2020 across Africa and identified reassortants using an automated Graph Incompatibility Based Reassortment Finder software. Viral reassortment rates were estimated using a coalescent reassortant constant population model. Phylogenetic analysis was used to assess the effect of reassortment on viral genetic evolution. We observed a high frequency of intra-subtype reassortment events, 12 · 4 per cent (94/758) and 20 · 9 per cent (256/1,224), and reassortants, 13 · 3 per cent (101/758) and 38 · 6 per cent (472/1,224), among Africa H1N1pdm09 and H3N2 viruses, respectively. H1N1pdm09 reassorted at higher rates (0.1237-0.4255) than H3N2 viruses (0 · 00912-0.0355 events/lineage/year), a case unique to Uganda. Viral reassortants were sampled in 2009 through 2020, except in 2012. 78 · 2 per cent (79/101) of H1N1pdm09 reassortants acquired new non-structural, while 57 · 8 per cent (273/472) of the H3N2 reassortants had new hemagglutinin (H3) genes. Africa H3N2 viruses underwent more reassortment events involving larger reassortant sets than H1N1pdm09 viruses. Viruses with a specific reassortment architecture circulated for up to five consecutive years in specific countries and regions. The Eastern (Uganda and Kenya) and Western Africa harboured 84 · 2 per cent (85/101) and 55 · 9 per cent (264/472) of the continent's H1N1pdm09 and H3N2 reassortants, respectively. The frequent reassortment involving multi-genes observed among Africa IAVs showed the intracontinental viral evolution and diversification possibly sustained by viral importation from outside Africa and/or local viral genomic mixing and transmission. Novel reassortant viruses emerged every year, and some persisted in different countries and regions, thereby presenting a risk of influenza outbreaks in Africa. Our findings highlight Africa as part of the global influenza ecology and the advantage of implementing routine whole-over partial genome sequencing and analyses to monitor circulating and detect emerging viruses. Furthermore, this study provides evidence and heightens our knowledge on IAV evolution, which is integral in directing vaccine strain selection and the update of master donor viruses used in recombinant vaccine development.
dc.format.mediumElectronic-eCollection
dc.publisherOxford University Press (OUP)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAfrica
dc.subjectH1N1pdm09
dc.subjectH3N2
dc.subjectUganda
dc.subjectevolution
dc.subjectgenomics
dc.subjectinfluenza A
dc.subjectintra-subtype reassortment
dc.subjectphylogenetics
dc.subjectreassortment
dc.subjecttransmission
dc.subjectwhole-genome sequencing
dc.titleWhole-genome analysis to determine the rate and patterns of intra-subtype reassortment among influenza type-A viruses in Africa.
dc.typeArticle
dc.publisher.departmentDepartment of Veterinary Medicine
dc.date.updated2022-04-21T10:12:19Z
prism.issueIdentifier1
prism.publicationDate2022
prism.publicationNameVirus Evol
prism.startingPageveac005
prism.volume8
dc.identifier.doi10.17863/CAM.83767
dcterms.dateAccepted2022-01-28
rioxxterms.versionofrecord10.1093/ve/veac005
rioxxterms.versionVoR
dc.contributor.orcidNabakooza, Grace [0000-0003-4565-3227]
dc.identifier.eissn2057-1577
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (107743/Z/15/Z)
cam.issuedOnline2022-01-29
cam.depositDate2022-04-21
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Except where otherwise noted, this item's licence is described as Attribution 4.0 International