RESUMO
Yellow fever virus (YFV) remains the cause of severe morbidity and mortality in South America and Africa. To determine the evolutionary history of this important reemerging pathogen, we performed a phylogenetic analysis of the largest YFV data set compiled to date, representing the prM/E gene region from 133 viral isolates sampled from 22 countries over a period of 76 years. We estimate that the currently circulating strains of YFV arose in Africa within the last 1,500 years and emerged in the Americas following the slave trade approximately 300-400 years ago. These viruses then spread westwards across the continent and persist there to this day in the jungles of South America. We therefore illustrate how gene sequence data can be used to test hypotheses of viral dispersal and demographics, and document the role of human migration in the spread of infectious disease.
Assuntos
Vírus da Febre Amarela/genética , África , Sequência de Bases , Bases de Dados de Ácidos Nucleicos , Emigração e Imigração , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Filogenia , América do Sul , Febre Amarela/história , Febre Amarela/transmissãoRESUMO
The 3' noncoding region (3' NCR) of flaviviruses contains secondary and tertiary structures essential for virus replication. Previous studies of yellow fever virus (YFV) and dengue virus have found that modifications to the 3' NCR are sometimes associated with attenuation in vertebrate and/or mosquito hosts. The 3' NCRs of 117 isolates of South American YFV have been examined, and major deletions and/or duplications of conserved RNA structures have been identified in several wild-type isolates. Nineteen isolates (designated YF-XL isolates) from Brazil, Trinidad, and Venezuela, dating from 1973 to 2001, exhibited a 216-nucleotide (nt) duplication, yielding a tandem repeat of conserved hairpin, stem-loop, dumbbell, and pseudoknot structures. YF-XL isolates were found exclusively within one subclade of South American genotype I YFV. One Brazilian isolate exhibited, in addition to the 216-nt duplication, a deletion of a 40-nt repeated hairpin (RYF) motif (YF-XL-DeltaRYF). To investigate the biological significance of these 3' NCR rearrangements, YF-XL-DeltaRYF and YF-XL isolates, as well as other South American YFV isolates, were evaluated for three phenotypes: growth kinetics in cell culture, neuroinvasiveness in suckling mice, and ability to replicate and produce disseminated infections in Aedes aegypti mosquitoes. YF-XL-DeltaRYF and YF-XL isolates showed growth kinetics and neuroinvasive characteristics comparable to those of typical South American YFV isolates, and mosquito infectivity trials demonstrated that both types of 3' NCR variants were capable of replication and dissemination in a laboratory-adapted colony of A. aegypti.
Assuntos
Camundongos , Animais , Humanos , Research Support, Non-U.S. Gov't , Research Support, U.S. Gov't, P.H.S. , Aedes/virologia , Sequência de Bases , Células Cultivadas , Variação Genética , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Filogenia , RNA não Traduzido/química , RNA não Traduzido/genética , RNA não Traduzido/fisiologia , RNA Viral/química , RNA Viral/genética , RNA Viral/fisiologia , Vírus da Febre Amarela/classificação , Vírus da Febre Amarela/crescimento & desenvolvimento , Vírus da Febre Amarela/genética , Vírus da Febre Amarela/isolamento & purificação , Vírus da Febre Amarela/patogenicidade , Trinidad e Tobago , Brasil , VenezuelaRESUMO
The 3' noncoding region (3' NCR) of flaviviruses contains secondary and tertiary structures essential for virus replication. Previous studies of yellow fever virus (YFV) and dengue virus have found that modifications to the 3' NCR are sometimes associated with attenuation in vertebrate and/or mosquito hosts. The 3' NCRs of 117 isolates of South American YFV have been examined, and major deletions and/or duplications of conserved RNA structures have been identified in several wild-type isolates. Nineteen isolates (designated YF-XL isolates) from Brazil, Trinidad, and Venezuela, dating from 1973 to 2001, exhibited a 216-nucleotide (nt) duplication, yielding a tandem repeat of conserved hairpin, stem-loop, dumbbell, and pseudoknot structures. YF-XL isolates were found exclusively within one subclade of South American genotype I YFV. One Brazilian isolate exhibited, in addition to the 216-nt duplication, a deletion of a 40-nt repeated hairpin (RYF) motif (YF-XL-DeltaRYF). To investigate the biological significance of these 3' NCR rearrangements, YF-XL-DeltaRYF and YF-XL isolates, as well as other South American YFV isolates, were evaluated for three phenotypes: growth kinetics in cell culture, neuroinvasiveness in suckling mice, and ability to replicate and produce disseminated infections in Aedes aegypti mosquitoes. YF-XL-DeltaRYF and YF-XL isolates showed growth kinetics and neuroinvasive characteristics comparable to those of typical South American YFV isolates, and mosquito infectivity trials demonstrated that both types of 3' NCR variants were capable of replication and dissemination in a laboratory-adapted colony of A. aegypti.
Assuntos
Variação Genética , RNA não Traduzido/genética , RNA Viral/genética , Vírus da Febre Amarela/genética , Vírus da Febre Amarela/isolamento & purificação , Aedes/virologia , Animais , Sequência de Bases , Células Cultivadas , Modelos Animais de Doenças , Camundongos , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Filogenia , RNA não Traduzido/química , RNA não Traduzido/fisiologia , RNA Viral/química , RNA Viral/fisiologia , Sequências Repetitivas de Ácido Nucleico , Deleção de Sequência , América do Sul , Febre Amarela/virologia , Vírus da Febre Amarela/classificação , Vírus da Febre Amarela/crescimento & desenvolvimento , Vírus da Febre Amarela/patogenicidadeRESUMO
An analysis of 79 yellow fever virus (YFV) isolates collected from 1935 to 2001 in Brazil showed a single genotype (South America I) circulating in the country, with the exception of a single strain from Rondonia, which represented South America genotype II. Brazilian YFV strains have diverged into two clades; an older clade appears to have become extinct and another has become the dominant lineage in recent years. Pairwise nucleotide diversity between strains ranged from 0% to 7.4%, while amino acid divergence ranged from 0% to 4.6%. Phylogenetic analysis indicated traffic of virus variants through large geographic areas and suggested that migration of infected people may be an important mechanism of virus dispersal. Isolation of vaccine virus from a patient with a fatal case suggests that vaccine-related illness may have been misdiagnosed in the past.
Assuntos
Variação Genética , Vírus da Febre Amarela/genética , Sequência de Aminoácidos , Brasil/epidemiologia , Evolução Molecular , Humanos , Epidemiologia Molecular , Filogenia , Alinhamento de Sequência , Febre Amarela/epidemiologia , Febre Amarela/virologiaRESUMO
We recently reported phylogenetic evidence to support the presence of enzootic transmission foci of yellow fever virus (YFV) in Peru [Bryant et al., Emerg. Infect. Dis. (2003)]. Because the prevailing paradigm of YFV transmission in Brazil is that of 'wandering epizootics' rather than discrete enzootic foci, we have now compared the molecular phylogenies of YFV isolates from Peru and Brazil, and re-examined the question of virus mobility by mapping the spatio-temporal distribution of genetic variants from these areas. Sequences were obtained for two genomic regions from 50 strains of YFV collected between 1954 and 2000 comprising 223 codons of the structural proteins (premembrane and envelope genes, 'prM/E'), and a distal region spanning the carboxy terminus of NS5 and part of the 3' non-coding region ('EMF'). Peruvian and Brazilian isolates formed two monophyletic clades with no evidence to support recombination between lineages. Variation within both coding and non-coding regions revealed similar substitution rates and overall levels of diversity within each clade. The branching structure of the prM/E and EMF trees of Brazilian sequences showed strong agreement of intra-lineage relationships; in contrast, the EMF sequences of Peruvian isolates failed to fully support the subclade structure of the prM/E phylogeny. These phylogenies suggest that transmission cycles of YFV in Peru and Brazil may sometimes be locally maintained within specific locales, but have also on occasion become very widely dispersed.