title: Single-cell mass cytometry analysis of human tonsil T cell remodeling by varicella zoster virus.
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.
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA 94025, USA.
authors.forename: Nandini
authors.initials: N
authors.lastname: Sen
authors.affiliation: Department of Statistics, Stanford University, Stanford, CA 94025, USA; Department of Data Sciences and Operations, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Gourab
authors.initials: G
authors.lastname: Mukherjee
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA 94025, USA.
authors.forename: Adrish
authors.initials: A
authors.lastname: Sen
authors.affiliation: Department of Microbiology and Immunology, Stanford University, Stanford, CA 94025, USA.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Bendall
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA 94025, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Sung
authors.affiliation: Department of Microbiology and Immunology, Stanford University, Stanford, CA 94025, USA.
authors.forename: Garry P
authors.initials: GP
authors.lastname: Nolan
authors.affiliation: 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.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Arvin
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D005434:Flow Cytometry; D014645:Herpesvirus 3, Human / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D008954:Models, Biological; D014066:Palatine Tonsil / Q000166:cytology* / Q000821:virology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D011948:Receptors, Antigen, T-Cell; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051057:Proto-Oncogene Proteins c-akt