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, 18 (6), 659-69

Evolution and Spread of Ebola Virus in Liberia, 2014-2015

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Evolution and Spread of Ebola Virus in Liberia, 2014-2015

Jason T Ladner et al. Cell Host Microbe.

Abstract

The 2013-present Western African Ebola virus disease (EVD) outbreak is the largest ever recorded with >28,000 reported cases. Ebola virus (EBOV) genome sequencing has played an important role throughout this outbreak; however, relatively few sequences have been determined from patients in Liberia, the second worst-affected country. Here, we report 140 EBOV genome sequences from the second wave of the Liberian outbreak and analyze them in combination with 782 previously published sequences from throughout the Western African outbreak. While multiple early introductions of EBOV to Liberia are evident, the majority of Liberian EVD cases are consistent with a single introduction, followed by spread and diversification within the country. Movement of the virus within Liberia was widespread, and reintroductions from Liberia served as an important source for the continuation of the already ongoing EVD outbreak in Guinea. Overall, little evidence was found for incremental adaptation of EBOV to the human host.

Figures

Figure 1
Figure 1
Temporal dynamics of the EVD outbreak in Liberia. (A) Confirmed and probable EVD cases in Liberia through time (WHO, 2015). (B) Temporal distribution of the 188 Liberian samples analyzed in this study. (C) Relative genetic diversity calculated with BEAST for the SL2 lineage in Liberia (SkyGrid reconstruction). The solid line represents the median estimate from the posterior probability, and the dashed lines represent the upper and lower estimates of the 95% credible interval.
Figure 2
Figure 2
Multiple early introductions of EBOV into Liberia. (A) Phylogenetic and temporal placement of 188 Liberian EBOV genomes relative to 734 EBOV sequences from Guinea, Mali and Sierra Leone. Three distinct lineages are represented in the Liberian samples: GN1, SL1 and SL2. (B) Median-joining haplotype network including 175 Liberian EBOV sequences with ≥97% genome coverage and 466 EBOV sequences representative of lineages circulating elsewhere in Western Africa.
Figure 3
Figure 3
Eight primary sub-lineages circulated during the second wave of EVD cases in Liberia. (A) Median-joining haplotype network based on a full genome alignment of 158 sequences from Liberia (SL2 only and with ≥98% genome coverage) and 95 sequences from Guinea and Mali that clustered within Liberian sub-lineages. (B) Root-to-tip distance versus testing date for each sub-lineage. (C) Geographic distribution of the Liberian sub-lineages, at the county-level within Liberia (white) and country-level outside Liberia (grey).
Figure 4
Figure 4
Widespread movement of EBOV during the second wave of the Liberian outbreak. (A) Temporal maximum clade credibility tree from BEAST analysis. Circles at the nodes indicate inferred ancestral location of each lineage. Circles with black outlines at the branch tips represent samples with known county of origin; those with white outlines were inferred in the analysis as a latent variable over the course of the MCMC. Circle size is proportional to the posterior probability of the assigned county. The bar at the root indicates the 95% HPD for the estimated root date. (B) Counts of exported vs imported viral lineages between locations across the posterior distribution. Vertical black lines indicate 95% HPD. (C) Well-supported (Bayes Factor ≥ 3) asymmetric rates of viral migration between counties. Arrow color indicates magnitude. Counties are colored by cumulative number of cases reported by the WHO. See also Figure S1.
Figure 5
Figure 5
Distribution of synonymous and non-synonymous substitutions within the open reading frames (ORFs) of the EBOV genome. Black lines below the ORFs (grey arrows) indicate the positions of codons with significant evidence of positive selection (Table S6). (A) Non-synonymous substitutions that have occurred within the Western African EVD outbreak (solid line) and between outbreaks caused by EBOV (dashed line). A sliding window of 1000 nucleotides (nt) was used with a step size of 250 nt. Each count was normalized by the average number of substitutions per window. (B & C) Distribution of dS (synonymous substitutions per synonymous site), dN (non-synonymous substitutions per non-synonymous site) and dN/dS. For each dataset, dS and dN were both normalized by the average dS per window. A sliding window of 999 nt (333 codons) was used with a step size of 249 nt (83 codons).
Figure 6
Figure 6
Liberian sub-lineages of EBOV contributed substantially to the largest peak in Guinean EVD cases. (A) The number of Guinean EBOV sequences through time colored based on the geographic origin of the evolutionary lineages to which each sequence belongs. (B) Confirmed and probable EVD cases in Guinea through time, according to the WHO’s patient database (WHO, 2015).

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