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.
Highlights
Yellow fever virus (YFV) is the causative agent of yellow fever (YF), a severe acute disease of historical importance that remains a major public health problem in endemic regions of South America and Africa[1, 2]
Likelihood (ML) phylogenetic analysis of YFV prM/E gene sequences revealed that all American isolates segregate in two reciprocally monophyletic clusters corresponding to genotypes I (n = 100) and II (n = 37) (Supplementary Fig. S1)
The mean evolutionary rates here estimated for YFV genotypes I and II were very similar among each other (~5 × 10−4 subs./site/yr) and fully consistent with those previously reported for YFV prM/E sequences of American and/or African origin (Table 1)[3, 13, 17, 18]
Summary
Yellow fever virus (YFV) is the causative agent of yellow fever (YF), a severe acute disease of historical importance that remains a major public health problem in endemic regions of South America and Africa[1, 2]. YFV strains currently circulating in South America branch within two distinct genotypes (I and II) that probably arose around the second half of the 19th century[10] These genotypes have diversified into several concurrent enzootic lineages that appear to persist and evolve within distinct geographic areas of Brazil, Bolivia, Peru, Trinidad and Tobago and Venezuela for long time periods[10,11,12,13,14,15]. While in situ evolution appears to be the predominant mechanism of YFV maintenance in South America and the Caribbean, some studies detected occasional YFV migrations between different American countries on long-time scales[13, 15] and others showed that YFV outbreaks were associated with the emergence of new lineages that replaced those causing previous outbreaks, as observed in the recent Brazilian epidemics (2000–2008)[10, 12]. We reconstructed the non-synonymous substitutions fixed along the entire genome of the ancestral virus from which the new YFV outbreaks occurring in the Americas evolved
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