Phylogenomic analysis of Uganda influenza type-A viruses to assess their relatedness to the vaccine strains and other Africa viruses: a molecular epidemiology study
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Date
2021
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bioRxiv
Abstract
Genetic characterisation of circulating influenza viruses is essential for vaccine
selection and mitigation of viral transmission. The current scantiness of viral genomic data and
underutilisation of advanced molecular analysis methods on influenza viruses circulating in Africa
has limited their extensive study and representation in the global influenza ecology. We aimed to
sequence influenza type-A viruses (IAVs) that previously circulated in Uganda and characterised
their genetic relatedness to the vaccine viruses and publicly available Africa IAVs.
Methods: This was an observational study nested to the Uganda national influenza surveillance
programme. We used Next-generation sequencing to locally generate genomes from 116
A(H1N1)pdm09 and 118 A(H3N2) viruses collected between 2010 and 2018 from 7 districts across
Uganda. A total of 206 hemagglutinin (HA), 207 neuraminidase (NA), and 213 matrix protein (MP)
sequences were genetically compared to the WHO-recommended vaccines and other viruses
isolated from Africa since 1994. Viral temporal and spatial divergence and circulating genetic clades
were characterised using phylogenetic methods.
Findings: We successfully generated gene sequences for 91·9% (215/234) viruses. Uganda
A(H1N1)pdm09 and A(H3N2) virus HA, NA, and MP proteins had 96·36-99·09%, 96·49-99·39%,
and 97·48-99·95% amino acid similarity, respectively, to vaccines recommended from 2010 through
2020. The local viruses incorporated amino acid substitutions (AAS) in their antigenic, receptor
binding, and glycosylation sites each year causing them to antigenically drift away from vaccines.
For seasons when vaccine formulations differed, Uganda IAV antigenic sites had 1-2 extra AAS
relative to the Southern than Northern hemisphere vaccine viruses. All Uganda IAVs carried the
adamantine-resistance marker S31N but not the neuraminidase inhibitor (NAI) resistance markers
H274Y and H275Y. However, some A(H1N1)pdm09 viruses had permissive substitutions V234I,
N369K, and V241I typical of NAI-resistant viruses.
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Nabakooza, G., Owuor, DC, de Laurent, ZR, Owor, N., Kayiwa, JT, Jjingo, D., ... & Lutwama, JJ (2021). Phylogenomic analysis of Uganda influenza type-A viruses to assess their relatedness to the vaccine strains and other Africa viruses: a molecular epidemiology study. bioRxiv . https://doi.org/10.1101/2021.07.05.451078