RESUMO
The yellow fever virus (YFV), the first proven human-pathogenic virus, although isolated in 1927, is still a major public health problem, especially in West Africa where it causes outbreaks every year. Nevertheless, little is known about its genetic diversity and evolutionary dynamics, mainly due to a limited number of genomic sequences from wild virus isolates. In this study, we analyzed the phylogenetic relationships of 24 full-length genomes from YFV strains isolated between 1973 and 2005 in a sylvatic context of West Africa, including 14 isolates that had previously not been sequenced. By this, we confirmed genetic variability within one genotype by the identification of various YF lineages circulating in West Africa. Further analyses of the biological properties of these lineages revealed differential growth behavior in human liver and insect cells, correlating with the source of isolation and suggesting host adaptation. For one lineage, repeatedly isolated in a context of vertical transmission, specific characteristics in the growth behavior and unique mutations of the viral genome were observed and deserve further investigation to gain insight into mechanisms involved in YFV emergence and maintenance in nature.
Assuntos
Genoma Viral , Vírus da Febre Amarela/classificação , Vírus da Febre Amarela/genética , Aedes/virologia , África Ocidental , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , Variação Genética , Genótipo , Células Hep G2 , Humanos , Insetos Vetores/virologia , Fígado/virologia , Dados de Sequência Molecular , Filogenia , RNA Viral/genética , Análise de Sequência de RNA , Proteínas Virais/química , Proteínas Virais/genética , Febre Amarela/genética , Febre Amarela/virologia , Vírus da Febre Amarela/isolamento & purificaçãoRESUMO
In recent years the safety of the yellow fever live vaccine 17D came under scrutiny. The focus was on serious adverse events after vaccinations that resemble a wild type infection with yellow fever and whose reasons are still not known. Also the exact mechanism of attenuation of the vaccine remains unknown to this day. In this context, the standards of safety and surveillance in vaccine production and administration have been discussed. Therein embodied was the demand for improved documentation of the derivation of the seed virus used for yellow fever vaccine production. So far, there was just a historical genealogy available that is based on source area and passage level. However, there is a need for a documentation based on molecular information to get better insights into the mechanisms of pathology. In this work we sequenced the whole genome of different passages of the YFV-17D strain used by Crucell Switzerland AG for vaccine production. Using all other publically available 17D full genome sequences we compared the sequence variance of all vaccine strains and oppose a phylogenetic tree based on full genome sequences to the historical genealogy.