Document Detail


Identification of cross-reactive norovirus CD4+ T cell epitopes.
MedLine Citation:
PMID:  20573810     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Immune responses and the components of protective immunity following norovirus infection in humans are poorly understood. Although antibody responses following norovirus infection have been partially characterized, T cell responses in humans remain largely undefined. In contrast, T cells have been shown to be essential for viral clearance of mouse norovirus (MNV) infection. In this paper, we demonstrate that CD4(+) T cells secrete gamma interferon (IFN-gamma) in response to stimulation with MNV virus-like particles (VLPs) after MNV infection, supporting earlier reports for norovirus-infected mice and humans. Utilizing this model, we immunized mice with alphavirus vectors (Venezuelan equine encephalitis [VEE] virus replicon particles [VRPs]) expressing Norwalk virus (NV) or Farmington Hills virus (FH) virus-like particles to evaluate T cell epitopes shared between human norovirus strains. Stimulation of splenocytes from norovirus VRP-immunized mice with overlapping peptides from complete libraries of the NV or FH capsid proteins revealed specific amino acid sequences containing T cell epitopes that were conserved within genoclusters and genogroups. Immunization with heterologous norovirus VRPs resulted in specific cross-reactive IFN-gamma secretion profiles following stimulation with NV and FH peptides in the mouse. Identification of unique strain-specific and cross-reactive epitopes may provide insight into homologous and heterologous T cell-mediated norovirus immunity and provide a platform for the study of norovirus-induced cellular immunity in humans.
Authors:
Anna D LoBue; Lisa C Lindesmith; Ralph S Baric
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-06-23
Journal Detail:
Title:  Journal of virology     Volume:  84     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-06     Completed Date:  2010-09-16     Revised Date:  2011-07-25    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8530-8     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, School of Medicine University of North Carolina at Chapel Hill, North Carolina 27599-7435, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
CD4-Positive T-Lymphocytes / immunology,  virology
Caliciviridae Infections / immunology*,  virology
Capsid Proteins / chemistry,  genetics,  immunology*
Cells, Cultured
Cross Reactions
Epitopes, T-Lymphocyte / chemistry,  genetics,  immunology*
Evolution, Molecular
Humans
Immunity, Cellular
Interferon-gamma / immunology
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Norovirus / chemistry,  genetics,  immunology*
Sequence Alignment
Species Specificity
Spleen / cytology,  immunology
Grant Support
ID/Acronym/Agency:
AI 056351-06/AI/NIAID NIH HHS; R01 AI056351-08/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Capsid Proteins; 0/Epitopes, T-Lymphocyte; 82115-62-6/Interferon-gamma
Comments/Corrections

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