The current reemergence of Yellow Fever virus (YFV) in the Southeastern Brazilian states is the largest and more devastating epizootic of jungle Yellow Fever registered in Brazil over the last 50 years. Regarding this outbreak, Bonaldo et al. (MEM INST OSWALDO CRUZ, 2017) have recently sequenced the whole YFV genome (accession numbers: KY885000 and KY885001) of two naturally infected howler-monkeys (Alouatta clamitans) from the State of Espírito Santo, one of the most currently affected states in Brazil. In the preliminary genetic classification of these YFV isolates, Bonaldo et al. noted that they clustered in 1E sub-clade of the South American genotype I. To gain new insights into the long-term evolutionary, demographic and phylogeographic dynamics of major YFV lineages circulating in the Americas, we used an up-to-date dataset, comprising YFV sequences sampled from nine South American and Caribbean countries between 1954 and 2017, including the two recently described YFV sequences from the Brazilian 2017 outbreak.
The rate of nucleotide substitution, the time to the most recent common ancestor (TMRCA) and the spatial diffusion pattern were jointly estimated using a Bayesian Markov-chain Monte Carlo approach using the non-parametric Bayesian skyline coalescent demographic model, a relaxed molecular clock and a reversible discrete phylogeographic model.
The spatiotemporal reconstruction suggested that the YFV genotype I likely originated in the Northern Brazilian region at around 1908 (95% Bayesian confidence interval (BCI): 1870–1936). Between 1940 and 1990, YFV genotype I spread from Northern Brazil to other Brazilian regions (Central-Western, Northeastern and Southeastern) and American countries (Colombia, Venezuela and Trinidad and Tobago) at multiple times. Several lineages co-circulated and diversified while spread through different countries and Brazilian regions, until the middle 1990s, when a dramatic change in the diversification process of the YFV genotype I occurred with the emergence of a new lineage (designated here as modern-lineage) that replaced old-lineages circulating in the previous decades (Fig. 1).
Fig.1 - Time-scaled Bayesian MCC tree of the YFV prM/E gene sequences. Branches are colored according to the most probable location state of their descendent nodes as indicated at the legend (top left). Triangles point to key nodes with high posterior probability support (PP>= 0.9). All horizontal branch lengths are drawn to a scale of years. The tree is automatically rooted under the assumption of a relaxed molecular clock. (AR: Argentina, BR-CO: Brazil Central-West, BR-N: Brazil North, BR-NE: Brazil Northeast,BR-S: Brazil South, BR-SE: Brazil Southeast, CO: Colombia, EC: Ecuador, PA: Panama, TT: Trinidad and Tobago, VE: Venezuela). Viral migration events occurred between 1908–1988 and 1989–2017 are summarized in the maps. Lines between locations represent branches in the Bayesian MCC tree along which location's transitions occur.
The modern-lineage comprises almost all YFV genotype I sequences isolated in the Americas after 1995. This lineage probably arose in Trinidad and Tobago at 1977 (95% BCI: 1964–1987) and was later concurrently disseminated to Northern Brazil and to Venezuela at 1989 (95% BCI: 1981–1996) and 1992 (95% BCI: 1986–1997), respectively. From Northern Brazil, the modern-lineage spread southward reaching other Brazilian regions. The introduction in Venezuela originated a sublineage that disseminated to Northern Brazil (originating sporadic human cases) and into Southeastern Brazil. The first introduction into the Southeastern Brazilian region was estimated at 2005 (95% BCI: 2002-2007), driving the 2008-2009 outbreak that later spread to Southern Brazil and Northern Argentina. The recent 2017 Brazilian outbreak seems to be an independent introduction event of the modern-lineage from Venezuela. The MRCA of the two Brazilian YFV strains sequences from 2017 was traced to 2016 (95% BCI: 2012-2017). The independent clustering of the sequences from the 2017 Brazilian outbreak indicate the introduction of a new lineage that may be replacing the former ones, however, more strains from the current Brazilian YFV epizootic/epidemic are necessary to confirm this hypothesis.
This work is part of an ongoing collaboration among researchers from Instituto Oswaldo Cruz/Fiocruz in Rio de Janeiro and a manuscript is under preparation, authored by:
Myrna C. Bonaldo2
Ana Carolina Vicente4
* Contributed equally
1 Laboratório de AIDS e Imunologia Molecular, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. 2 Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. 3 Laboratório de Mosquitos Transmissores de Hematozoários, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. 4 Laboratório de Genética Molecular de Microrganismos, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.