Details

Autor(en) / Beteiligte

• Sen, Nandini
• Mukherjee, Gourab
• Sen, Adrish
• Bendall, Sean C.
• Sung, Phillip
• Nolan, Garry P.
• Arvin, Ann M.

Titel

Single-Cell Mass Cytometry Analysis of Human Tonsil T Cell Remodeling by Varicella Zoster Virus

Ist Teil von

• Cell reports (Cambridge), 2014-07, Vol.8 (2), p.633-645

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Application of single-cell mass cytometry to study virus-host interactions•CyTOF analysis of Varicella-infected human tonsil T cells using 40+ parameters•Development of statistical method to determine remodeling in differentiated cells•Observation that varicella-zoster virus uses T cell plasticity to support pathogenesis Single-cell mass cytometry with multiparametric data analysis permits proteomic deep profiling based on combinatorial expression of many proteins in each cell. Sen et al. now demonstrate that primary human tonsil T cells are remodeled by VZV infection, regardless of their basal phenotypic and functional states, to a configuration promoting viral transport to skin. This approach should be useful in showing how other intracellular pathogens alter the heterogeneous properties of differentiated host cells to support pathogenesis.