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Cell Rep. 2014 Jul 24;8(2):633-45. doi: 10.1016/j.celrep.2014.06.024. Epub 2014 Jul 17.

Single-cell mass cytometry analysis of human tonsil T cell remodeling by varicella zoster virus.

Author information

1
Department of Pediatrics, Stanford University, Stanford, CA 94025, USA.
2
Department of Statistics, Stanford University, Stanford, CA 94025, USA; Department of Data Sciences and Operations, University of Southern California, Los Angeles, CA 90089, USA.
3
Department of Medicine, Stanford University, Stanford, CA 94025, USA.
4
Department of Microbiology and Immunology, Stanford University, Stanford, CA 94025, USA.
5
Department of Pediatrics, Stanford University, Stanford, CA 94025, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94025, USA. Electronic address: aarvin@stanford.edu.

Abstract

Although pathogens must infect differentiated host cells that exhibit substantial diversity, documenting the consequences of infection against this heterogeneity is challenging. Single-cell mass cytometry permits deep profiling based on combinatorial expression of surface and intracellular proteins. We used this method to investigate varicella-zoster virus (VZV) infection of tonsil T cells, which mediate viral transport to skin. Our results indicate that VZV induces a continuum of changes regardless of basal phenotypic and functional T cell characteristics. Contrary to the premise that VZV selectively infects T cells with skin trafficking profiles, VZV infection altered T cell surface proteins to enhance or induce these properties. Zap70 and Akt signaling pathways that trigger such surface changes were activated in VZV-infected naive and memory cells by a T cell receptor (TCR)-independent process. Single-cell mass cytometry is likely to be broadly relevant for demonstrating how intracellular pathogens modulate differentiated cells to support pathogenesis in the natural host.

PMID:
25043183
PMCID:
PMC4127309
DOI:
10.1016/j.celrep.2014.06.024
[Indexed for MEDLINE]
Free PMC Article

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