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Methods. 2015 Nov 15;90:85-94. doi: 10.1016/j.ymeth.2015.07.008. Epub 2015 Jul 23.

Single cell mass cytometry reveals remodeling of human T cell phenotypes by varicella zoster virus.

Author information

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

Abstract

The recent application of mass cytometry (CyTOF) to biology provides a 'systems' approach to monitor concurrent changes in multiple host cell factors at the single cell level. We used CyTOF to evaluate T cells infected with varicella zoster virus (VZV) infection, documenting virus-mediated phenotypic and functional changes caused by this T cell tropic human herpesvirus. Here we summarize our findings using two complementary panels of antibodies against surface and intracellular signaling proteins to elucidate the consequences of VZV-mediated perturbations on the surface and in signaling networks of infected T cells. CyTOF data was analyzed by several statistical, analytical and visualization tools including hierarchical clustering, orthogonal scaling, SPADE, viSNE, and SLIDE. Data from the mass cytometry studies demonstrated that VZV infection led to 'remodeling' of the surface architecture of T cells, promoting skin trafficking phenotypes and associated with concomitant activation of T-cell receptor and PI3-kinase pathways. This method offers a novel approach for understanding viral interactions with differentiated host cells important for pathogenesis.

KEYWORDS:

Single Cell Linkage using Distance Estimation (SLIDE); Single cell mass cytometry; T cell remodeling by VZV; VZV lymphotropism

PMID:
26213183
PMCID:
PMC4655147
DOI:
10.1016/j.ymeth.2015.07.008
[Indexed for MEDLINE]
Free PMC Article

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