Significant Impact of Sequence Variations in the Nucleoprotein on CD8 T Cell-Mediated Cross-Protection against Influenza A Virus Infections

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Significant Impact of Sequence Variations in the Nucleoprotein on CD8 T Cell-Mediated Cross-Protection against Influenza A Virus Infections

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Title: Significant Impact of Sequence Variations in the Nucleoprotein on CD8 T Cell-Mediated Cross-Protection against Influenza A Virus Infections
Author: Zhong, Weimin; Dong, Libo; Lu, Xiuhua; Hancock, Kathy; Katz, Jacqueline M.; Sambhara, Suryaprakash; Liu, Feng; Reinherz, Ellis Leonard

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Citation: Zhong, Weimin, Feng Liu, Libo Dong, Xiuhua Lu, Kathy Hancock, Ellis L. Reinherz, Jacqueline M. Katz, and Suryaprakash Sambhara. 2010. Significant impact of sequence variations in the nucleoprotein on CD8 T cell-mediated cross-protection against influenza A virus infections. PLoS ONE 5(5): e10583.
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Abstract: Background: Memory CD8 T cells to influenza A viruses are widely detectable in healthy human subjects and broadly cross-reactive for serologically distinct influenza A virus subtypes. However, it is not clear to what extent such pre-existing cellular immunity can provide cross-subtype protection against novel emerging influenza A viruses. Methodology/Principal: Findings We show in the mouse model that naturally occurring sequence variations of the conserved nucleoprotein of the virus significantly impact cross-protection against lethal disease in vivo. When priming and challenge viruses shared identical sequences of the immunodominant, protective NP366/Db epitope, strong cross-subtype protection was observed. However, when they did not share complete sequence identity in this epitope, cross-protection was considerably reduced. Contributions of virus-specific antibodies appeared to be minimal under these circumstances. Detailed analysis revealed that the magnitude of the memory CD8 T cell response triggered by the NP366/Db variants was significantly lower than those triggered by the homologous NP366/Db ligand. It appears that strict specificity of a dominant public TCR to the original NP366/Db ligand may limit the expansion of cross-reactive memory CD8 T cells to the NP366/Db variants. Conclusions/Significance: Pre-existing CD8 T cell immunity may provide substantial cross-protection against heterosubtypic influenza A viruses, provided that the priming and the subsequent challenge viruses share the identical sequences of the immunodominant, protective CTL epitopes.
Published Version: doi:10.1371/journal.pone.0010583
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868023/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4859265
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