Flavitrack: an annotated database of flavivirus sequences

Misra, Milind; Schein, Catherine H.

doi:10.1093/bioinformatics/btm383

Cited by 22 publications

(19 citation statements)

References 13 publications

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“…2a and 2b) substitution has been documented in another WNV isolate from France (2000)(Fig. 2a) that contains the threonine residue at the NS3-249 position [32], [33]. The introduction of a histidine could assist in stabilizing the NS3 hydrophobic loop moiety when a threonine is present at the NS3-249 residue, but further studies are needed to characterize the role of stabilization of the hydrophobic domain as a function of avian peripheral replication.…”

Section: Discussionmentioning

confidence: 86%

Host Competence and Helicase Activity Differences Exhibited by West Nile Viral Variants Expressing NS3-249 Amino Acid Polymorphisms

et al. 2014

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A single helicase amino acid substitution, NS3-T249P, has been shown to increase viremia magnitude/mortality in American crows (AMCRs) following West Nile virus (WNV) infection. Lineage/intra-lineage geographic variants exhibit consistent amino acid polymorphisms at this locus; however, the majority of WNV isolates associated with recent outbreaks reported worldwide have a proline at the NS3-249 residue. In order to evaluate the impact of NS3-249 variants on avian and mammalian virulence, multiple amino acid substitutions were engineered into a WNV infectious cDNA (NY99; NS3-249P) and the resulting viruses inoculated into AMCRs, house sparrows (HOSPs) and mice. Differential viremia profiles were observed between mutant viruses in the two bird species; however, the NS3-249P virus produced the highest mean peak viral loads in both avian models. In contrast, this avian modulating virulence determinant had no effect on LD50 or the neurovirulence phenotype in the murine model. Recombinant helicase proteins demonstrated variable helicase and ATPase activities; however, differences did not correlate with avian or murine viremia phenotypes. These in vitro and in vivo data indicate that avian-specific phenotypes are modulated by critical viral-host protein interactions involving the NS3-249 residue that directly influence transmission efficiency and therefore the magnitude of WNV epizootics in nature.

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Section: Discussionmentioning

confidence: 86%

Host Competence and Helicase Activity Differences Exhibited by West Nile Viral Variants Expressing NS3-249 Amino Acid Polymorphisms

et al. 2014

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“…The Flavitrack database 17; 18 contains more than 2000 annotated, complete flavivirus genomes, of which 928 natural isolates were used in this study. The E and NS3 sequences were obtained for 10 mosquito-borne, 13 tick-borne and 4 no-known-vector (NKV; sequences of viruses isolated from bats or rodents that have not been found in insects) species; annotated according to CDC abbreviations (http://www.ncid.cdc.gov/arbocat/browse.asp).…”

Section: Methodsmentioning

confidence: 99%

“…We tested a new method for defining consensus sequences, based on conservation of physicochemical properties (PCPs) at each position of correctly aligned sequences (where the alignment was checked to insure that it was consistent with the tertiary structure of the protein). The basis of our work was the cross-referenced database of annotated FV sequences, Flavitrack (http://carnot.utmb.edu/flavitrack) 17; 18. Using this information resource, we aligned and analyzed 928 naturally occurring (i.e, we excluded vaccine strains or lab-made chimeras) strains of 27 flavivirus species.…”

Section: Introductionmentioning

confidence: 99%

PCP Consensus Sequences of Flaviviruses: Correlating Variance with Vector Competence and Disease Phenotype

Danecek

Schein

2010

Journal of Molecular Biology

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“…Here we will show some applications based on data stored in our Flavitrack database (http://carnot.utmb.edu/flavitrack), which is a compendium of annotated Flavivirus sequences [9,10]. Flaviviruses (FV), which include yellow fever (YFV), DENV, and West Nile viruses (WNV), are important human and animal pathogens which typically require insect vectors to infect mammalian hosts [30-35].…”

Section: Resultsmentioning

confidence: 99%

Physicochemical property consensus sequences for functional analysis, design of multivalent antigens and targeted antivirals

et al. 2012

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BackgroundAnalysis of large sets of biological sequence data from related strains or organisms is complicated by superficial redundancy in the set, which may contain many members that are identical except at one or two positions. Thus a new method, based on deriving physicochemical property (PCP)-consensus sequences, was tested for its ability to generate reference sequences and distinguish functionally significant changes from background variability.MethodsThe PCP consensus program was used to automatically derive consensus sequences starting from sequence alignments of proteins from Flaviviruses (from the Flavitrack database) and human enteroviruses, using a five dimensional set of Eigenvectors that summarize over 200 different scalar values for the PCPs of the amino acids. A PCP-consensus protein of a Dengue virus envelope protein was produced recombinantly and tested for its ability to bind antibodies to strains using ELISA.ResultsPCP-consensus sequences of the flavivirus family could be used to classify them into five discrete groups and distinguish areas of the envelope proteins that correlate with host specificity and disease type. A multivalent Dengue virus antigen was designed and shown to bind antibodies against all four DENV types. A consensus enteroviral VPg protein had the same distinctive high pKa as wild type proteins and was recognized by two different polymerases.ConclusionsThe process for deriving PCP-consensus sequences for any group of aligned similar sequences, has been validated for sequences with up to 50% diversity. Ongoing projects have shown that the method identifies residues that significantly alter PCPs at a given position, and might thus cause changes in function or immunogenicity. Other potential applications include deriving target proteins for drug design and diagnostic kits.

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Flavitrack: an annotated database of flavivirus sequences

Cited by 22 publications

References 13 publications

Host Competence and Helicase Activity Differences Exhibited by West Nile Viral Variants Expressing NS3-249 Amino Acid Polymorphisms

Host Competence and Helicase Activity Differences Exhibited by West Nile Viral Variants Expressing NS3-249 Amino Acid Polymorphisms

PCP Consensus Sequences of Flaviviruses: Correlating Variance with Vector Competence and Disease Phenotype

Physicochemical property consensus sequences for functional analysis, design of multivalent antigens and targeted antivirals

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