scholarly journals Exploratory re-encoding of yellow fever virus genome: new insights for the design of live-attenuated viruses

2018 ◽  
Vol 4 (2) ◽  
Author(s):  
R Klitting ◽  
T Riziki ◽  
G Moureau ◽  
G Piorkowski ◽  
E A Gould ◽  
...  
2012 ◽  
Vol 50 (12) ◽  
pp. 4054-4060 ◽  
Author(s):  
C. Domingo ◽  
P. Patel ◽  
J. Yillah ◽  
M. Weidmann ◽  
J. A. Mendez ◽  
...  

2013 ◽  
Vol 85 (1) ◽  
pp. 159-168 ◽  
Author(s):  
Sabrina R.A. Queiroz ◽  
Andréa N.M.R. Silva ◽  
Jefferson J.S. Santos ◽  
Ernesto T.A. Marques Jr ◽  
Giovani R. Bertani ◽  
...  

RNA replicon derived from Flavivirus genome is a valuable tool for studying viral replication independent of virion assembly and maturation, besides being a great potencial for heterologous gene expression. In this study we described the construction of subgenomic replicons of yellow fever virus by yeast-based homologous recombination technique. The plasmid containing the yellow fever 17D strain replicon (pBSC-repYFV-17D), previously characterized, was handled to heterologous expression of the green fluorescent protein (repYFV-17D-GFP) and firefly luciferase (repYFV-17D-Luc) reporter genes. Both replicons were constructed by homologous recombination between the linearized vector pBSC-repYFV-17D and the PCR product containing homologous 25 nucleotides ends incorporated into PCR primers. The genomic organization of these constructs is similar to repYFV-17D, but with insertion of the reporter gene between the remaining 63 N-terminal nucleotides of the capsid protein and 72 C-terminal nucleotides of the E protein. The replicons repYFV-17D-GFP and repYFV-17D-Luc showed efficient replication and expression of the reporter genes. The yeast-based homologous recombination technique used in this study proved to be applicable for manipulation of the yellow fever virus genome in order to construct subgenomic replicons.


2011 ◽  
Vol 174 (1-2) ◽  
pp. 29-34 ◽  
Author(s):  
Marcio R.T. Nunes ◽  
Gustavo Palacios ◽  
Keley N.B. Nunes ◽  
Samir M.M. Casseb ◽  
Lívia C. Martins ◽  
...  

2020 ◽  
Vol 7 (2) ◽  
Author(s):  
My V T Phan ◽  
Mariana Mendonca Melo ◽  
Els van Nood ◽  
Georgina Aron ◽  
Jolanda J C Kreeft-Voermans ◽  
...  

Abstract We report yellow fever infection in a Dutch traveler returning from Brazil. Yellow fever virus (YFV) was identified in serum and urine samples over a period of 1 month. Yellow fever virus genome sequences from the patient clustered with recent Brazilian YFV and showed with limited nucleotide changes during the resolving infection.


2018 ◽  
Author(s):  
R. Klitting ◽  
T. Riziki ◽  
G. Moureau ◽  
G. Piorkowski ◽  
E. A. Gould ◽  
...  

AbstractVirus attenuation by genome re-encoding is a pioneering approach for generating effective live-attenuated vaccine candidates. Its core principle is to introduce a large number of synonymous substitutions into the viral genome to produce stable attenuation of the targeted virus. Introduction of large numbers of mutations has also been shown to maintain stability of the attenuated phenotype by lowering the risk of reversion and recombination of re-encoded genomes. Identifying mutations with low fitness cost is pivotal as this increases the number that can be introduced and generates more stable and attenuated viruses. Here, we sought to identify mutations with low deleterious impact on thein vivoreplication and virulence of yellow fever virus (YFV). Following comparative bioinformatic analyses of flaviviral genomes, we categorized synonymous transition mutations according to their impact on CpG/UpA composition and secondary RNA structures. We then designed 17 re-encoded viruses with 100-400 synonymous mutations in the NS2A-to-NS4B coding region of YFVAsibiandAp7M(hamster-adapted) genomes. Each virus contained a panel of synonymous mutations designed according to the above categorisation criteria. The replication and fitness characteristics of parent and re-encoded viruses were comparedin vitrousing cell culture competition experiments.In vivolaboratory hamster models were also used to compare relative virulence and immunogenicity characteristics. Most of the re-encoded strains showed no decrease in replicative fitnessin vitro. However, they showed reduced virulence and, in some instances, decreased replicative fitnessin vivo. Importantly, the most attenuated of the re-encoded strains induced robust, protective immunity in hamsters following challenge withAp7M, a virulent virus. Overall, the introduction of transitions with no or a marginal increase in the number of CpG/UpA dinucleotides had the mildest impact on YFV replication and virulencein vivo. Thus, this strategy can be incorporated in procedures for the finely tuned creation of substantially re-encoded viral genomes.


2021 ◽  
Vol 6 ◽  
pp. 664-677
Author(s):  
Tara Sadeghieh ◽  
Jan M. Sargeant ◽  
Amy L. Greer ◽  
Olaf Berke ◽  
Guillaume Dueymes ◽  
...  

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1475
Author(s):  
Moussa Moïse Diagne ◽  
Marie Henriette Dior Ndione ◽  
Alioune Gaye ◽  
Mamadou Aliou Barry ◽  
Diawo Diallo ◽  
...  

Yellow fever virus remains a major threat in low resource countries in South America and Africa despite the existence of an effective vaccine. In Senegal and particularly in the eastern part of the country, periodic sylvatic circulation has been demonstrated with varying degrees of impact on populations in perpetual renewal. We report an outbreak that occurred from October 2020 to February 2021 in eastern Senegal, notified and managed through the synergistic effort yellow fever national surveillance implemented by the Senegalese Ministry of Health in collaboration with the World Health Organization, the countrywide 4S network set up by the Ministry of Health, the Institut Pasteur de Dakar, and the surveillance of arboviruses and hemorrhagic fever viruses in human and vector populations implemented since mid 2020 in eastern Senegal. Virological analyses highlighted the implication of sylvatic mosquito species in virus transmission. Genomic analysis showed a close relationship between the circulating strain in eastern Senegal, 2020, and another one from the West African lineage previously detected and sequenced two years ago from an unvaccinated Dutch traveler who visited the Gambia and Senegal before developing signs after returning to Europe. Moreover, genome analysis identified a 6-nucleotide deletion in the variable domain of the 3′UTR with potential impact on the biology of the viral strain that merits further investigations. Integrated surveillance of yellow fever virus but also of other arboviruses of public health interest is crucial in an ecosystem such as eastern Senegal.


1929 ◽  
Vol 92 (7) ◽  
pp. 550 ◽  
Author(s):  
HENRIQUE DE BEAUREPAIRE ARAGÃO

1995 ◽  
Vol 35 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Claudia N. Duarte dos Santos ◽  
Paulo R. Post ◽  
Ricardo Carvalho ◽  
Idevaldo I. Ferreira ◽  
Charles M. Rice ◽  
...  

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