Phylodynamics of Yellow Fever Virus in the Americas: new insights into the origin of the 2017 Brazilian outbreak

Abstract

Yellow fever virus (YFV) strains circulating in the Americas belong to two distinct genotypes (I and II) that have diversified into several concurrent enzootic lineages. Since 1999, YFV genotype I has spread outside endemic regions and its recent (2017) reemergence in non-endemic Southeastern Brazilian states fuels one of the largest epizootic of jungle Yellow Fever registered in the country. To better understand this phenomenon, we reconstructed the phylodynamics of YFV American genotypes using sequences from nine countries sampled along 60 years, including strains from Brazilian 2017 outbreak. Our analyses reveals that YFV genotypes I and II follow roughly similar evolutionary and demographic dynamics until the early 1990s, when a dramatic change in the diversification process of the genotype I occurred associated with the emergence and dissemination of a new lineage (here called modern). Trinidad and Tobago was the most likely source of the YFV modern-lineage that spread to Brazil and Venezuela around the late 1980s, where it replaced all lineages previously circulating. The modern-lineage caused all major YFV outbreaks detected in non-endemic South American regions since 2000, including the 2017 Brazilian outbreak, and its dissemination was coupled to the accumulation of several amino acid substitutions particularly within non-structural viral proteins.

What Does the Future Hold for Yellow Fever Virus? (I)

“…In this genotype, the "Old" lineage, comprises the Old Para, 1A, 1B, and 1C sub-lineages that have progressively been replaced by "Modern" sublineages. The currently prevailing "Modern" lineage emerged in Trinidad and Tobago in the 1980s and now consists of the Trinidad and Tobago, 1D and 1E sub-lineages [143,145]. Similarly, lineage replacement occurred within the "Modern" lineage as observed during the epidemic of 2008-2009 in Rio Grande do Sul and Sao Paulo.…”

“…The existing molecular data regarding genotype circulation in Africa show dynamics that are constrained by the presence of both hosts and vectors, with the formation of discrete epidemic foci [142,143]. However, some examples of co-circulation can be found in the outbreaks of 1983 and 1985 in Burkina Faso, caused by the Western and West/Central genotypes, respectively [142].…”

“…Much remains to be learned concerning the circulation dynamics of YFV in Africa and the Americas largely because the data available for phylogenetic analysis of YFV isolates are scarce and viral samples are rarely preserved for genetic studies [143,146,147].…”

“…Similarly, lineage replacement occurred within the "Modern" lineage as observed during the epidemic of 2008-2009 in Rio Grande do Sul and Sao Paulo. This outbreak was caused by the emergent sub-lineage 1E, that successfully replaced its ancestral sub-lineage, 1D and now prevails in the region [109,142,143].…”

“…They had probably emerged by the end of the 19 th century [142] and subsequently diversified to produce several lineages that are associated with distinct geographic areas (Brazil, Columbia, Bolivia, Peru, Trinidad/ Tobago and Venezuela). YFV circulation dynamics in South America (and the Caribbean) are characterized by both local circulation associated with in situ evolution [136,143] and occasional circulation across Latin American countries [68,136] with frequent lineage replacement from outbreak to outbreak. Lineage replacement is a particularly important phenomenon in the evolution of South American genotype I [144].…”