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Discovery of common marburgvirus protective epitopes in a BALB/c mouse model
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Discovery of common marburgvirus protective epitopes in a BALB/c mouse model
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Discovery of common marburgvirus protective epitopes in a BALB/c mouse model
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Journal Article
Discovery of common marburgvirus protective epitopes in a BALB/c mouse model
2009
Overview
Background
Marburg virus (MARV) causes acute hemorrhagic fever that is often lethal, and no licensed vaccines are available for preventing this deadly viral infection. The immune mechanisms for protection against MARV are poorly understood, but previous studies suggest that both antibodies and T cells are required. In our study, we infected BALB/c mice with plaque-purified, nonlethal MARV and used overlapping peptides to map H2
d
-restricted CD8+ T-cell epitopes.
Methods
Splenocytes from mice infected with nonlethal MARV were harvested and stimulated with multiple overlapping 15-mer peptide pools, and reactive CD8+ T cells were evaluated for antigen specificity by measuring upregulation of CD44 and interferon-γ expression. After confirming positive reactivity to specific 15-mer peptides, we used extrapolated 9-mer epitopes to evaluate the induction of cytotoxic T-cell responses and protection from lethal MARV challenge in BALB/c mice.
Results
We discovered a CD8+ T-cell epitope within both the MARV glycoprotein (GP) and nucleoprotein (NP) that triggered cytotoxic T-cell responses. These responses were also protective when epitope-specific splenocytes were transferred into naïve animals.
Conclusion
Epitope mapping of MARV GP, NP, and VP40 provides the first evidence that specific MARV-epitope induction of cellular immune responses is sufficient to combat infection. Establishment of CD8+ T-cell epitopes that are reactive to MARV proteins provides an important research tool for dissecting the significance of cellular immune responses in BALB/c mice infected with MARV.
Publisher
BioMed Central,BioMed Central Ltd,BMC
Subject
/ Animals
/ Biomedical and Life Sciences
/ CD8-Positive T-Lymphocytes - chemistry
/ CD8-Positive T-Lymphocytes - immunology
/ Epitopes, T-Lymphocyte - chemistry
/ Epitopes, T-Lymphocyte - immunology
/ Humans
/ Marburg Virus Disease - immunology
/ Marburg Virus Disease - prevention & control
/ Marburg Virus Disease - virology
/ Mice
/ Viral Envelope Proteins - chemistry
/ Viral Envelope Proteins - immunology
/ Virology
