Flavitrack Analysis of the Structure and Function of West Nile Non-structural
Proteins
The Flavitrack database was developed to relate the
sequences of the Flaviviridae to the phenotype of the viruses,
to aid in design of vaccines and specific antivirals. Statistical
methods were developed to compare the genomes of the Flaviviruses,
which are evolutionarily closely related organisms with
high subtype variability. Due to the variability within each virus
group, methods that compare randomly selected representatives
from each of the virus groups can give misleading results. Here,
statistically rigorous methods were used to analyze all available
sequences for each group separately. The resulting consensus
sequences were then used to calculate motifs based on conserved
physicochemical properties. In the application illustrated here,
the tools were used to compare 919 sequences of NS2a, one of the
viral proteins that block the host interferon response to infection.
The analysis indicated that residues, which if altered in Kunjin
(West Nile) sequence, reduced the ability of the virus to grow and
prevented it from blocking interferon production, are all in the
conserved N-terminus. One possible model, based on a nuclear
receptor protein structure, placed three of these residues (I59,
V61, M103) close to one another in a negatively charged pocket
on the protein surface.
Index Terms
Consensus sequence, Flavitrack, NS2a, PCPMer, West Nile virus.