Yellow fever virus maintenance in Trinidad and its dispersal throughout the Americas

Abstract

Trinidad, like many other American regions, experiences repeated epizootics of yellow fever virus (YFV). However, it is unclear whether these result from in situ evolution (enzootic maintenance) or regular reintroduction of YFV from the South American mainland. To discriminate between these hypotheses, we carried out a Bayesian phylogeographic analysis of over 100 prM/E gene sequences sampled from 8 South American countries. These included newly sequenced isolates from the recent 2008-2009 Trinidad epizootic and isolates derived from mainland countries within the last decade. The results indicate that the most recent common ancestor of the 2008-2009 epizootic existed in Trinidad 4.2 years prior to 2009 (95% highest probability density [HPD], 0.5 to 9.0 years). Our data also suggest a Trinidad origin for the progenitor of the 1995 Trinidad epizootic and support in situ evolution of YFV between the 1979 and 1988-1989 Trinidad epizootics. Using the same phylogeographic approach, we also inferred the historical spread of YFV in the Americas. The results suggest a Brazilian origin for YFV in the Americas and an overall dispersal rate of 182 km/year (95% HPD, 52 to 462 km/year), with Brazil as the major source population for surrounding countries. There is also strong statistical support for epidemiological links between four Brazilian regions and other countries. In contrast, while there were well-supported epidemiological links within Peru, the only statistically supported external link was a relatively weak link with neighboring Bolivia. Lastly, we performed a complete analysis of the genome of a newly sequenced Trinidad 2009 isolate, the first complete genome for a genotype I YFV isolate.

FIG. 1.

Bayesian MCC tree for YFV in the Americas, based on prM/E gene fragment of 654 nt. Taxon labels include year of isolation, strain designation, and country of isolation. Terminal branches of the tree are colored according to the sampled location of the taxon at the tip. Internal branches are colored according to the most probable (modal) location of their parental node. Nodes with posterior probabilities (clade credibilities) of ≥0.95 have been labeled accordingly (in black). The probabilities of the modal locations of selected nodes are shown in blue (as percentages). The date of divergence (with 95% HPD in parentheses) of the 2009 Trinidad isolates is highlighted in gray. The histogram insert shows the posterior probabilities for the locations of the root nodes.

FIG. 2.

MCC tree showing the inferred introductions into Trinidad from the mainland. Introductions are indicated by the wide orange branches. Terminal branches of the tree are colored according to the sampled location state of the taxon at the tip, and internal branches are colored according to the most probable (modal) geographic location state of the nodes supporting them. The branch thickness represents the median posterior jump count to Trinidad (the values are plotted along the four thick branches).

FIG. 3.

Snapshots of dispersal patterns among countries (a) and among regions (b) at 20-year intervals from 1928 to 2008. Lines between locations represent branches in the MCC tree along which the relevant location transition occurs. Location circle diameters are proportional to the square root of the number of MCC branches maintaining a particular location state at each time point. The blue-purple color gradient indicates the relative ages of the transitions (older-recent). The maps are based on satellite pictures made available by Google Earth.

FIG. 4.

BF test for significant nonzero rates. Rates supported by a BF of >3 are shown for the “among-country” (a) and “among-region” (b) analyses. The color and thickness of the line represent the relative strength by which the rates are supported; thin white lines and thick red lines suggest relatively weak and strong support, respectively. The maps are based on satellite pictures made available by Google Earth.