scholarly journals Size Heterogeneity in the 3′ Noncoding Region of South American Isolates of Yellow Fever Virus

2005 ◽  
Vol 79 (6) ◽  
pp. 3807-3821 ◽  
Author(s):  
Juliet E. Bryant ◽  
Pedro F. C. Vasconcelos ◽  
Rene C. A. Rijnbrand ◽  
J. P. Mutebi ◽  
Stephen Higgs ◽  
...  

ABSTRACT 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-ΔRYF). To investigate the biological significance of these 3′ NCR rearrangements, YF-XL-ΔRYF 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-ΔRYF 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.

2010 ◽  
Vol 82 (1) ◽  
pp. 175-185 ◽  
Author(s):  
Renato P. de Souza ◽  
Peter G. Foster ◽  
Maria Anice M. Sallum ◽  
Terezinha L.M. Coimbra ◽  
Adriana Y. Maeda ◽  
...  

2004 ◽  
Vol 78 (18) ◽  
pp. 9652-9665 ◽  
Author(s):  
John-Paul Mutebi ◽  
René C. A. Rijnbrand ◽  
Heiman Wang ◽  
Kate D. Ryman ◽  
Eryu Wang ◽  
...  

ABSTRACT Genetic relationships among flaviviruses within the yellow fever (YF) virus genetic group were investigated by comparing nucleotide sequences of the 3′ noncoding region (3′NCR). Size heterogeneity was observed between members and even among strains of the same viral species. Size variation between YF strains was due to duplications and/or deletions of repeated nucleotide sequence elements (RYF). West African genotypes had three copies of the RYF (RYF1, RYF2, and RYF3); the Angola and the East and Central African genotypes had two copies (RYF1 and RYF3); and South American genotypes had only a single copy (RYF3). Nucleotide sequence analyses suggest a deletion within the 3′NCR of South American genotypes, including RYF1 and RYF2. Based on studies with the French neurotropic vaccine strain, passage of a YF virus strain in cell culture can result in deletion of RYF1 and RYF2. Taken together, these observations suggest that South American genotypes of YF virus evolved from West African genotypes and that the South American genotypes lost RYF1 and RYF2, possibly in a single event. Repeated sequence elements were found within the 3′NCR of other members of the YF virus genetic group, suggesting that it is probably characteristic for members of the YF virus genetic group. A core sequence of 15 nucleotides, containing two stem-loops, was found within the 3′NCR of all members of the YF genetic group and may represent the progenitor repeat sequence. Secondary structure predictions of the 3′NCR showed very similar structures for viruses that were closely related phylogenetically.


2007 ◽  
Vol 88 (6) ◽  
pp. 1738-1747 ◽  
Author(s):  
Patrícia A. G. C. Silva ◽  
Richard Molenkamp ◽  
Tim J. Dalebout ◽  
Nathalie Charlier ◽  
Johan H. Neyts ◽  
...  

The pentanucleotide (PN) sequence 5′-CACAG-3′ at the top of the 3′ stem–loop structure of the flavivirus genome is well conserved in the arthropod-borne viruses but is more variable in flaviviruses with no known vector. In this study, the sequence requirements of the PN motif for yellow fever virus 17D (YFV) replication were determined. In general, individual mutations at either the second, third or fourth positions were tolerated and resulted in replication-competent virus. Mutations at the fifth position were lethal. Base pairing of the nucleotide at the first position of the PN motif and a nucleotide four positions downstream of the PN (ninth position) was a major determinant for replication. Despite the fact that the majority of the PN mutants were able to replicate efficiently, they were outcompeted by parental YFV-17D virus following repeated passages in double-infected cell cultures. Surprisingly, some of the virus mutants at the first and/or the ninth position that maintained the possibility of forming a base pair were found to have a similar fitness to YFV-17D under these conditions. Overall, these experiments suggest that YFV is less dependent on sequence conservation of the PN motif for replication in animal cells than West Nile virus. However, in animal cell culture, YFV has a preference for the wt CACAG PN sequence. The molecular mechanisms behind this preference remain to be elucidated.


2010 ◽  
Vol 84 (19) ◽  
pp. 9967-9977 ◽  
Author(s):  
Albert J. Auguste ◽  
Philippe Lemey ◽  
Oliver G. Pybus ◽  
Marc A. Suchard ◽  
Rosa Alba Salas ◽  
...  

ABSTRACT Trinidad, like many other American regions, experiences repeated epizootics of yellow fever virus (YFV). However, it is unclear whether these result from in situ evolution (enzootic maintenance) or regular reintroduction of YFV from the South American mainland. To discriminate between these hypotheses, we carried out a Bayesian phylogeographic analysis of over 100 prM/E gene sequences sampled from 8 South American countries. These included newly sequenced isolates from the recent 2008-2009 Trinidad epizootic and isolates derived from mainland countries within the last decade. The results indicate that the most recent common ancestor of the 2008-2009 epizootic existed in Trinidad 4.2 years prior to 2009 (95% highest probability density [HPD], 0.5 to 9.0 years). Our data also suggest a Trinidad origin for the progenitor of the 1995 Trinidad epizootic and support in situ evolution of YFV between the 1979 and 1988-1989 Trinidad epizootics. Using the same phylogeographic approach, we also inferred the historical spread of YFV in the Americas. The results suggest a Brazilian origin for YFV in the Americas and an overall dispersal rate of 182 km/year (95% HPD, 52 to 462 km/year), with Brazil as the major source population for surrounding countries. There is also strong statistical support for epidemiological links between four Brazilian regions and other countries. In contrast, while there were well-supported epidemiological links within Peru, the only statistically supported external link was a relatively weak link with neighboring Bolivia. Lastly, we performed a complete analysis of the genome of a newly sequenced Trinidad 2009 isolate, the first complete genome for a genotype I YFV isolate.


Virology ◽  
1996 ◽  
Vol 225 (2) ◽  
pp. 274-281 ◽  
Author(s):  
Eryu Wang ◽  
Scott C. Weaver ◽  
Robert E. Shope ◽  
Robert B. Tesh ◽  
Douglas M. Watts ◽  
...  

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