Acute emergence and reversion of influenza A virus quasispecies within CD8( ) Tcell antigenic peptides
Sophie A Valkenburg, Sergio Quinones-Parra, Stephanie Gras, Naomi Komadina, Jodie McVernon, Zhongfang Wang, Hanim Halim, Pina Iannello, Catherine Cole, Karen Laurie, Anne Kelso, Jamie Rossjohn, Peter C Doherty, Stephen J Turner, Katherine Kedzierska
NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2013
Influenza A virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) provide a degree of cross-strain protection that is potentially subverted by mutation. Here we describe the sequential emergence of such variants within CTL epitopes for a persistently infected, immunocompromised infant. Further analysis in immunodeficient and wild-type mice supports the view that CTL escape variants arise frequently in influenza, accumulate with time and revert in the absence of immune pressure under MHCI-mismatched conditions. Viral fitness, the abundance of endogenous CD8(+) T cell responses and T cell receptor repertoire diversity influence the nature of these de novo mutants. Structural characterization of..View full abstract
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Awarded by Australian National Health and Medical Research Council (NHMRC)
Awarded by NHMRC
We thank Miss Kathrin Gartner for the expert technical assistance in generating selected plasmid constructs. This work was supported by Australian National Health and Medical Research Council (NHMRC) Project Grant to K. K. (AI1008854), an NHMRC Program Grant (AI567122) to P. C. D., A. K. and S.J.T. S. A. V. is an NHMRC Overseas Biomedical Research Fellow, K. K. is an NHMRC CDF2 Fellow, Z.W. is an NHMRC Australia-China Exchange Fellow, S.J.T. is an ARC Future Fellow (Level 3), S. G. is an ARC Future Fellow (Level 1), J.R. is an NHMRC Australian Fellow and S. Q. P. is a recipient of the University of Melbourne International Research Scholarship and CONACyT Scholar. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health and Ageing.