Single-Cell Mass Cytometry Analysis of Human Tonsil T Cell Remodeling by Varicella Zoster Virus
Open accessAbstract
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.
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The scale and precision of single-cell studies has continued to increase, reaching tens of thousands of cells for massively parallel scRNA-seq and millions of cells for mass cytometry protein measurements.
“The scale and precision of such studies has continued to increase, reaching tens of thousands of cells for massively parallel scRNA-seq30,31 and millions of cells for mass cytometry signature protein measurements32–34.”
From Revealing the vectors of cellular identity with single-cell genomics (2016) · cites this paper as [33]
Using the latest protocols for massively parallel scRNA-seq and mass cytometry, a single laboratory can now readily collect tens of thousands to hundreds of thousands of single-cell RNA-seq profiles and tens of millions of single-cell protein profiles.
“Using the latest protocols for massively parallel scRNA-seq30,31 and mass cytometry32–34, a single laboratory can now readily collect tens of thousands to hundreds of thousands of single-cell RNA-seq profiles and tens of millions of single-cell protein profiles.”
From Revealing the vectors of cellular identity with single-cell genomics (2016) · cites this paper as [33]
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Self-citation
- Authors
- Sen, N., Mukherjee, G., Sen, A., Bendall, S. C., Sung, P., Nolan, G. P., & Arvin, A. M.
- Affiliations
- Stanford Medicine (US)
- University of Southern California (US)
- Stanford University (US)
- Corresponding author
- Arvin, Ann M.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 8
- Issue
- 2
- Pages
- 633-645
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4127309
- OpenAlex
- W2048139582
- Cited by
- 90
- References
- 37
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 6 · 2018: 15 · 2017: 12 · 2016: 15 · 2015: 9 · 2014: 3
- FWCI
- 9.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (5u54ca143907-05)
- U.S. Public Health Service (NIH 5-24927, NIH 41000411217)
- National Heart, Lung, and Blood Institute (N01-HV 00242)
- National Eye Institute (PN2EY018228)
- National Cancer Institute (5U54CA143907NIH, U54CA149145, U54-CA-143907, R01CA130826, P01CA034233)
- National Institute of General Medical Sciences (K99GM104148, R00GM104148)
- National Institute of Allergy and Infectious Diseases (R01AI053846, R01AI020459, AI05346, R37AI020459, NIH AI20459, U19AI057229)
- National Institute of Biomedical Imaging and Bioengineering (R01EB001988, NIH R01 EB 001988)
- Topics
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- varicella-zoster virus, T cell migration, skin-homing T cells, Akt signaling, naive and memory T cells, intracellular pathogens, single-cell mass cytometry
- MeSH terms
- Cell Differentiation, Cells, Cultured, Flow Cytometry, Humans, Models, Biological, Receptors, Antigen, T-Cell, T-Lymphocytes, Palatine Tonsil, Herpesvirus 3, Human, Signal Transduction, Proto-Oncogene Proteins c-akt, ZAP-70 Protein-Tyrosine Kinase, Host-Pathogen Interactions
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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