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Genomic epidemiology and evolutionary dynamics of respiratory syncytial virus group B in Kilifi, Kenya, 2015-17
Everlyn Kamau
James R Otieno
Nickson Murunga
John W Oketch
Joyce M Ngoi
Zaydah R. de Laurent
Anthony Mwema
Joyce U Nyiro
Charles N Agoti
D James Nokes
Novel Coronavirus
Acceso Abierto
Atribución-SinDerivadas
10.1101/2020.03.08.20032920
Respiratory syncytial virus (RSV) circulates worldwide and is a leading cause of acute respiratory illness in young children. There is paucity of genomic data from purposively sampled populations by which to investigate evolutionary dynamics and transmission patterns of RSV. Here we present an analysis of 295 RSV group B genomes from Kilifi, coastal Kenya, sampled from individuals seeking outpatient care in 9 health facilities across a defined geographical area (890 km2), over 2 RSV epidemics between 2015 and 2017. RSVB diversity was characterized by multiple viral introductions into the area and co-circulation of distinct genetic groups or clusters, which transmitted and diversified locally but with varying frequency. Bayesian analyses indicated a strong spatially and temporally structured viral population suggesting extensive within-epidemic virus transmission. Phylogeographic analysis provided a strong support for epidemiological linkage from one central health facility to other facilities. Increase in relative diversity paralleled increase in seasonal viral incidence. Importantly, we identified a cluster of viruses (n=91) that emerged in the 2016/17 epidemic, carrying distinct amino-acid signatures including a novel non-synonymous change (K68Q) in antigenic site θ in the Fusion gene. A different non-synonymous change K68N was recently associated with escape from a potent neutralizing monoclonal antibody (MEDI8897). RSVB diversity was additionally marked by signature non-synonymous substitutions that were unique to particular genomic clusters, some of which were under diversifying selection. Our findings provide insights into recent evolutionary and epidemiologic behaviors of RSV group B, and highlight possible emergence of a novel antigenic variant, which has implications on current prophylactic development strategies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Wellcome Trust [grant 102975, 203077]. CNA is supported by the Initiative to Develop African Research Leaders (IDeAL) through the DELTAS Africa Initiative [DEL-15-003]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [107769/Z/10/Z] and the UK government. The views expressed in this publication are those of the authors and not necessarily those of AAS, NEPAD Agency, Wellcome Trust or the UK government. ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The replication data and analysis scripts for this manuscript are available from the Harvard Dataverse. Genome sequences have been submitted to GenBank.
Cold Spring Harbor Laboratory Press
2020
Preimpreso
https://www.medrxiv.org/content/10.1101/2020.03.08.20032920v1
Inglés
VIRUS RESPIRATORIOS
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