Conservation and variability of West Nile virus proteins

Qi Ying Koo, Asif M. Khan, Keun Ok Jung, Shweta Ramdas, Olivo Miotto, Tin Wee Tan, Vladimir Brusic, Jerome Salmon, J. Thomas August

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

West Nile virus (WNV) has emerged globally as an increasingly important pathogen for humans and domestic animals. Studies of the evolutionary diversity of the virus over its known history will help to elucidate conserved sites, and characterize their correspondence to other pathogens and their relevance to the immune system. We describe a large-scale analysis of the entire WNV proteome, aimed at identifying and characterizing evolutionarily conserved amino acid sequences. This study, which used 2,746 WNV protein sequences collected from the NCBI GenPept database, focused on analysis of peptides of length 9 amino acids or more, which are immunologically relevant as potential T-cell epitopes. Entropy-based analysis of the diversity of WNV sequences, revealed the presence of numerous evolutionarily stable nonamer positions across the proteome (entropy value of ≤1). The representation (frequency) of nonamers variant to the predominant peptide at these stable positions was, generally, low (≤10% of the WNV sequences analyzed). Eighty-eight fragments of length 9-29 amino acids, representing ∼34% of the WNV polyprotein length, were identified to be identical and evolutionarily stable in all analyzed WNV sequences. Of the 88 completely conserved sequences, 67 are also present in other flaviviruses, and several have been associated with the functional and structural properties of viral proteins. Immunoinformatic analysis revealed that the majority (78/88) of conserved sequences are potentially immunogenic, while 44 contained experimentally confirmed human T-cell epitopes. This study identified a comprehensive catalogue of completely conserved WNV sequences, many of which are shared by other flaviviruses, and majority are potential epitopes. The complete conservation of these immunologically relevant sequences through the entire recorded WNV history suggests they will be valuable as components of peptide-specific vaccines or other therapeutic applications, for sequence-specific diagnosis of a wide-range of Flavivivirus infections, and for studies of homologous sequences among other flaviviruses.

Original languageEnglish
Article numbere5352
JournalPLoS One
Volume4
Issue number4
DOIs
Publication statusPublished - Apr 29 2009
Externally publishedYes

Fingerprint

West Nile virus
Viruses
Conservation
Flaviviridae
Flavivirus
Proteins
proteins
epitopes
T-Lymphocyte Epitopes
conserved sequences
Conserved Sequence
Entropy
peptides
Proteome
entropy
proteome
Pathogens
Amino Acids
Peptides
amino acid sequences

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Koo, Q. Y., Khan, A. M., Jung, K. O., Ramdas, S., Miotto, O., Tan, T. W., ... August, J. T. (2009). Conservation and variability of West Nile virus proteins. PLoS One, 4(4), [e5352]. https://doi.org/10.1371/journal.pone.0005352

Conservation and variability of West Nile virus proteins. / Koo, Qi Ying; Khan, Asif M.; Jung, Keun Ok; Ramdas, Shweta; Miotto, Olivo; Tan, Tin Wee; Brusic, Vladimir; Salmon, Jerome; August, J. Thomas.

In: PLoS One, Vol. 4, No. 4, e5352, 29.04.2009.

Research output: Contribution to journalArticle

Koo, QY, Khan, AM, Jung, KO, Ramdas, S, Miotto, O, Tan, TW, Brusic, V, Salmon, J & August, JT 2009, 'Conservation and variability of West Nile virus proteins', PLoS One, vol. 4, no. 4, e5352. https://doi.org/10.1371/journal.pone.0005352
Koo QY, Khan AM, Jung KO, Ramdas S, Miotto O, Tan TW et al. Conservation and variability of West Nile virus proteins. PLoS One. 2009 Apr 29;4(4). e5352. https://doi.org/10.1371/journal.pone.0005352
Koo, Qi Ying ; Khan, Asif M. ; Jung, Keun Ok ; Ramdas, Shweta ; Miotto, Olivo ; Tan, Tin Wee ; Brusic, Vladimir ; Salmon, Jerome ; August, J. Thomas. / Conservation and variability of West Nile virus proteins. In: PLoS One. 2009 ; Vol. 4, No. 4.
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