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. 2020 Jul 15;6(2):veaa050.
doi: 10.1093/ve/veaa050. eCollection 2020 Jul.

Genomic epidemiology and evolutionary dynamics of respiratory syncytial virus group B in Kilifi, Kenya, 2015-17

Everlyn Kamau  1 , James R Otieno  1 , Nickson Murunga  1 , John W Oketch  1 , Joyce M Ngoi  1 , Zaydah R de Laurent  1 , Anthony Mwema  1 , Joyce U Nyiro  1 , Charles N Agoti  1   2 , D James Nokes  1   3
Affiliations

Genomic epidemiology and evolutionary dynamics of respiratory syncytial virus group B in Kilifi, Kenya, 2015-17

Everlyn Kamau et al. Virus Evol. .

Abstract

Respiratory syncytial virus (RSV) circulates worldwide, occurring seasonally in communities, 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 (RSVB) genomes from Kilifi, coastal Kenya, sampled from individuals seeking outpatient care in nine health facilities across a defined geographical area (∼890 km2), over two RSV epidemics between 2015 and 2017. RSVB diversity was characterized by multiple virus introductions into the area and co-circulation of distinct genetic clusters, which transmitted and diversified locally with varying frequency. Increase in relative genetic diversity paralleled seasonal virus incidence. Importantly, we identified a cluster of viruses that emerged in the 2016/17 epidemic, carrying distinct amino-acid signatures including a novel nonsynonymous change (K68Q) in antigenic site ∅ in the Fusion protein. RSVB diversity was additionally marked by signature nonsynonymous substitutions that were unique to particular genomic clusters, some under diversifying selection. Our findings provide insights into recent evolutionary and epidemiological behaviors of RSVB, and highlight possible emergence of a novel antigenic variant, which has implications on current prophylactic strategies in development.

Keywords: RSV; community; emergence; evolution; genomes.

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Figures

Figure 1.
Figure 1.
A map showing the geographical area covered in the KHDSS, expanded from a map of Kenya. The nine participating public health facilities are indicated in the map. The dark lines within the polygons indicate the road structure within KHDSS. The maps were rendered using QGIS 2.18.17 (https://www.qgis.org/).
Figure 2.
Figure 2.
Monthly RSVB occurrence by study location: temporal and spatial distribution of RSVB positive cases (left Y axis) and number of clinical samples tested (right Y axis) from each participating health facilities. Abbreviations: CHA, Chasimba; JAR, Jaribuni; JUN, Junju; MAV, Mavueni; MAT, Matsangoni; PIN, Pingilikani; NGE, Ngerenya; SOK, Sokoke; MTO, Mtondia.
Figure 3.
Figure 3.
(A) Relative frequencies of potential nonsynonymous changes across codon-aligned RSV genome sequences. The frequencies for each codon position are calculated as the number of nonsynonymous nucleotide substitutions for all pairwise comparisons in a sequence alignment, while excluding ambiguous bases or insertions. Abbreviations: CT, cytoplasmic; TM, transmembrane; CCD, central conserved domain; SP, signal peptide; RdRp, RNA-dependent RNA polymerase; Cap, capping; and MT, methyltransferase; CD, connector domain; CTD, C-terminal domain. (B) Bayesian skygrid analysis depicting fluctuating relative genetic diversity for the two RSV epidemics. Solid line represents mean relative genetic diversity while the corresponding dashed lines indicate the 95 per cent HPD intervals.
Figure 4.
Figure 4.
MCC phylogenies inferred for 573 viruses sampled globally between 2012 and 2017. (A) Temporal structure of the Kilifi genomes with tip colors indicating the sampling period (RSV epidemic). Clade assignments are indicated as I to VI, similarly to Supplementary Table S2. Node support is indicated by posterior probability values. (B) MCC tree similar to (A) but showing the spatial patterns of the RSVB introductions in Kilifi, Kenya with tips indicating the sampling location. In both phylogenies, sequences from outside Kilifi are colored black.
Figure 5
Figure 5
(A) Root-to-tip genetic distances as a function of sampling time. (B) Estimates of the mean and 95 per cent HPD interval of the substitution rate (substitution/site/year) from the real/actual dataset (bordered by dashed line), and from the ten datasets generated by clustered permutation of sampling dates.
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