Tracing the origin of the NS1 A188V substitution responsible for recent enhancement of Zika virus Asian genotype infectivity

<div><p>A recent study showed that infectivity of Zika virus (ZIKV) Asian genotype was enhanced by an alanine-to-valine amino acid substitution at residue 188 of the NS1 protein, but the precise time and location of origin of this mutation were not formally estimated. Here, we applied a Bayesian coalescent-based framework to estimate the age and location of the ancestral viral strain carrying the A188V substitution. Our results support that the ancestral ZIKV strain carrying the A188V substitution arose in Southeastern Asia at the early 2000s and circulated in that region for some time (5-10 years) before being disseminated to Southern Pacific islands and the Americas.</p></div

Spatiotemporal Dynamics of the HIV-1 Subtype G Epidemic in West and Central Africa

<div><p>The human immunodeficiency virus type 1 (HIV-1) subtype G is the second most prevalent HIV-1 clade in West Africa, accounting for nearly 30% of infections in the region. There is no information about the spatiotemporal dynamics of dissemination of this HIV-1 clade in Africa. To this end, we analyzed a total of 305 HIV-1 subtype G <i>pol</i> sequences isolated from 11 different countries from West and Central Africa over a period of 20 years (1992 to 2011). Evolutionary, phylogeographic and demographic parameters were jointly estimated from sequence data using a Bayesian coalescent-based method. Our analyses indicate that subtype G most probably emerged in Central Africa in 1968 (1956–1976). From Central Africa, the virus was disseminated to West and West Central Africa at multiple times from the middle 1970s onwards. Two subtype G strains probably introduced into Nigeria and Togo between the middle and the late 1970s were disseminated locally and to neighboring countries, leading to the origin of two major western African clades (G_WA-I and G_WA-II). Subtype G clades circulating in western and central African regions displayed an initial phase of exponential growth followed by a decline in growth rate since the early/middle 1990s; but the mean epidemic growth rate of G_WA-I (0.75 year⁻¹) and G_WA-II (0.95 year⁻¹) clades was about two times higher than that estimated for central African lineages (0.47 year⁻¹). Notably, the overall evolutionary and demographic history of G_WA-I and G_WA-II clades was very similar to that estimated for the CRF06_cpx clade circulating in the same region. These results support the notion that the spatiotemporal dissemination dynamics of major HIV-1 clades circulating in western Africa have probably been shaped by the same ecological factors.</p></div

HIV-1 subtype G <i>pol</i> dataset.

a<p>Location assigned in the Bayesian phylogeographic analysis. DRC: Democratic Republic of Congo.</p

Time-scaled Bayesian MCC tree of the HIV-1 subtype G <i>pol</i> PR/RT sequences (∼1,000 nt) circulating in West and Central Africa.

<p>Branches are colored according to the most probable location state of their descendent nodes as indicated at the legend (bottom left). Arcs indicate the positions of major subtype G clades characteristic of western (G_WA-I and G_WA-II) and central (G_CA) African regions. Asterisks point to key nodes with high posterior state probability support (<i>PSP</i>>0.85). Branch lengths are drawn to scale of years. The tree was automatically rooted under the assumption of a relaxed molecular clock.</p

HIV-1 subtype G <i>pol</i> dataset.

a<p>Location assigned in the Bayesian phylogeographic analysis. DRC: Democratic Republic of Congo.</p

Spatiotemporal dynamics of HIV-1 subtype G clade dissemination in West and Central Africa.

<p>Snapshots of viral migration events occurring at different time intervals between 1970 and 2012 are shown. Lines between locations represent branches in the Bayesian MCC tree along which location transitions occur. Each location is represented by a color as indicated at the legend. SN: Senegal; TG/GH: Togo/Ghana; BJ: Benin; NG: Nigeria; CM: Cameroon; GA/GQ: Gabon/Equatorial Guinea; AO/CD/CG: Angola/DRC/Republic of Congo.</p

Prevalence of G_WA-I, G_WA-II and G_CA clades among subtype G infected individuals from different African countries, estimated from phylogenetic analyses presented in Figs. 1 and S1.

<p>The total number of subtype G sequences analyzed in each locality is indicated. Each clade is represented by a color as indicated at the legend.</p

Viral migration rates among locations as measured using ‘Markov jump’ counts.

<p>Each panel represents the estimated viral exchanges from and to Angola/DRC/Republic of Congo (A), Cameroon (B), Gabon/Equatorial Guinea (C), Benin (D), Togo/Ghana (E), Nigeria (F), and Senegal (G). The width of the arrows is proportional to the corresponding mean estimated number of viral transitions between locations according to the following scale: thin arrows = 1.0–2.9 transitions, medium arrows = 3.0–5.9 transitions, thick arrows = 6.0–8.9 transitions. No arrows were displayed when the mean estimated number of transitions was below one.</p

Demographic history of the HIV-1 subtype G and the clades G_CA, G_WA-I and G_WA-II circulating in Central and West Africa.

<p>Effective number of infections (y-axis; log10 scale) through time (x-axis; calendar years) estimated using Bayesian skyline (A, B, D, F) and logistic (C, E, G) growth coalescent model. Median estimates of the effective number of infections (solid line) and 95% HPD intervals of the estimates (dashed lines) are shown in each graphic. The median growth rate (with the corresponding 95% credibility interval in parenthesis) of each clade estimated under the logistic growth model is indicated in the upper left corner.</p

Spatiotemporal Dynamics of DENV-2 Asian-American Genotype Lineages in the Americas

<div><p>The Asian/American (AS/AM) genotype of dengue virus type 2 (DENV-2) has been evolving in the Americas over the last 30 years, leading to several waves of dengue epidemics and to the emergence of different viral lineages in the region. In this study, we investigate the spatiotemporal dissemination pattern of the DENV-2 lineages at a regional level. We applied phylogenetic and phylogeographic analytical methods to a comprehensive data set of 582 DENV-2 E gene sequences of the AS/AM genotype isolated from 29 different American countries over a period of 30 years (1983 to 2012). Our study reveals that genetic diversity of DENV-2 AS/AM genotype circulating in the Americas mainly resulted from one single founder event and can be organized in at least four major lineages (I to IV), which emerged in the Caribbean region at the early 1980s and then spread and die out with different dynamics. Lineages I and II dominate the epidemics in the Caribbean region during the 1980s and early 1990s, lineage III becomes the prevalent DENV-2 one in the Caribbean and South America during the 1990s, whereas lineage IV dominates the epidemics in South and Central America during the 2000s. Suriname and Guyana seem to represent important entry points for DENV-2 from the Lesser Antilles to South America, whereas Venezuela, Brazil and Nicaragua were pointed as the main secondary hubs of dissemination to other mainland countries. Our study also indicates that DENV-2 AS/AM genotype was disseminated within South America following two main routes. The first route hits Venezuela and the western side of the Andes, while the second route mainly hits Brazil and the eastern side of the Andes. The phenomenon of DENV-2 lineage replacement across successive epidemic outbreaks was a common characteristic in all American countries, although the timing of lineage replacements greatly vary across locations.</p></div