PMID- 22573867
OWN - NLM
STAT- MEDLINE
DCOM- 20120910
LR  - 20211021
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 86
IP  - 14
DP  - 2012 Jul
TI  - West Nile virus T-cell ligand sequences shared with other flaviviruses: a 
      multitude of variant sequences as potential altered peptide ligands.
PG  - 7616-24
LID - 10.1128/JVI.00166-12 [doi]
AB  - Phylogenetic relatedness and cocirculation of several major human pathogen 
      flaviviruses are recognized as a possible cause of deleterious immune responses 
      to mixed infection or immunization and call for a greater understanding of the 
      inter-Flavivirus protein homologies. This study focused on the identification of 
      human leukocyte antigen (HLA)-restricted West Nile virus (WNV) T-cell ligands and 
      characterization of their distribution in reported sequence data of WNV and other 
      flaviviruses. H-2-deficient mice transgenic for either A2, A24, B7, DR2, DR3, or 
      DR4 HLA alleles were immunized with overlapping peptides of the WNV proteome, and 
      peptide-specific T-cell activation was measured by gamma interferon (IFN-gamma) 
      enzyme-linked immunosorbent spot (ELISpot) assays. Approximately 30% (137) of the 
      WNV proteome peptides were identified as HLA-restricted T-cell ligands. The 
      majority of these ligands were conserved in  approximately >/=88% of analyzed WNV sequences. 
      Notably, only 51 were WNV specific, and the remaining 86, chiefly of E, NS3, and 
      NS5, shared an identity of nine or more consecutive amino acids with sequences of 
      64 other flaviviruses, including several major human pathogens. Many of the 
      shared ligands had an incidence of >50% in the analyzed sequences of one or more 
      of six major flaviviruses. The multitude of WNV sequences shared with other 
      flaviviruses as interspecies variants highlights the possible hazard of defective 
      T-cell activation by altered peptide ligands in the event of dual exposure to WNV 
      and other flaviviruses, by either infection or immunization. The data suggest the 
      possible preferred use of sequences that are pathogen specific with minimum 
      interspecies sequence homology for the design of Flavivirus vaccines.
FAU - Jung, Keun-Ok
AU  - Jung KO
AD  - Department of Pharmacology and Molecular Sciences, The Johns Hopkins University 
      School of Medicine, Baltimore, MD, USA.
FAU - Khan, Asif M
AU  - Khan AM
FAU - Tan, Benjamin Yong Liang
AU  - Tan BY
FAU - Hu, Yongli
AU  - Hu Y
FAU - Simon, Gregory G
AU  - Simon GG
FAU - Nascimento, Eduardo J M
AU  - Nascimento EJ
FAU - Lemonnier, Francois
AU  - Lemonnier F
FAU - Brusic, Vladimir
AU  - Brusic V
FAU - Miotto, Olivo
AU  - Miotto O
FAU - Tan, Tin Wee
AU  - Tan TW
FAU - Marques, Ernesto T A
AU  - Marques ET
FAU - Dhalia, Rafael
AU  - Dhalia R
FAU - Salmon, Jerome
AU  - Salmon J
FAU - August, J Thomas
AU  - August JT
LA  - eng
PT  - Journal Article
DEP - 20120509
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, Viral)
RN  - 0 (Histocompatibility Antigens)
RN  - 0 (Ligands)
RN  - 0 (Proteome)
RN  - 0 (Viral Proteins)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antigens, Viral/*immunology
MH  - Enzyme-Linked Immunospot Assay
MH  - Flavivirus/*immunology
MH  - Genetic Variation
MH  - Histocompatibility Antigens/genetics/*immunology
MH  - Interferon-gamma
MH  - Ligands
MH  - *Lymphocyte Activation
MH  - Mice
MH  - Mice, Transgenic
MH  - Proteome
MH  - T-Lymphocytes/*immunology/metabolism
MH  - Viral Proteins/*immunology
MH  - West Nile virus/genetics/*immunology/metabolism
PMC - PMC3416302
EDAT- 2012/05/11 06:00
MHDA- 2012/09/11 06:00
PMCR- 2013/01/01
CRDT- 2012/05/11 06:00
PHST- 2012/05/11 06:00 [entrez]
PHST- 2012/05/11 06:00 [pubmed]
PHST- 2012/09/11 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - JVI.00166-12 [pii]
AID - 00166-12 [pii]
AID - 10.1128/JVI.00166-12 [doi]
PST - ppublish
SO  - J Virol. 2012 Jul;86(14):7616-24. doi: 10.1128/JVI.00166-12. Epub 2012 May 9.