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Published on: September 1, 2015
Mass Cytometric Analysis of HIV Entry, Replication, and Remodeling in Tissue CD4+ T Cells
Marielle Cavrois1, Trambak Banerjee2, Gourab Mukherjee2
1Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Insights
Researchers identified a specific subset of memory CD4+ T cells that allow HIV entry but not replication. These long-lived CD127+ T cells are found in HIV-infected patients but show limited viral activity.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Understanding HIV susceptibility is crucial for developing effective prevention and treatment strategies.
- Identifying specific T cell subsets involved in HIV infection provides insights into viral pathogenesis.
Purpose of the Study:
- To characterize CD4+ T cell subsets susceptible to HIV infection.
- To identify which CD4+ T cell populations support HIV fusion and productive infection using advanced phenotyping.
Main Methods:
- Single-cell mass cytometry (CyTOF) was used to phenotype infected tonsillar T cells.
- Dimensionality reduction, clustering, and statistical analyses were employed to compare HIV-fused and HIV-infected cells.
- Analytical approaches distinguished selective infection from viral receptor modulation.
Main Results:
- A subset of memory CD4+ T cells was identified that supports HIV entry but not viral gene expression.
- These cells express high levels of CD127 (the IL-7 receptor) and are long-lived lymphocytes.
- In HIV-infected patients, CD127-expressing cells were found in extrafollicular regions with limited viral replication.
Conclusions:
- CyTOF-based phenotyping is a valuable discovery tool for characterizing viral susceptibility in specific cell subsets.
- CD127+ memory CD4+ T cells represent a distinct population with implications for HIV persistence and viral reservoirs.
Abstract:
To characterize susceptibility to HIV infection, we phenotyped infected tonsillar T cells by single-cell mass cytometry and created comprehensive maps to identify which subsets of CD4+ T cells support HIV fusion and productive infection. By comparing HIV-fused and HIV-infected cells through dimensionality reduction, clustering, and statistical approaches to account for viral perturbations, we identified a subset of memory CD4+ T cells that support HIV entry but not viral gene expression. These cells express high levels of CD127, the IL-7 receptor, and are believed to be long-lived lymphocytes. In HIV-infected patients, CD127-expressing cells preferentially localize to extrafollicular lymphoid regions with limited viral replication. Thus, CyTOF-based phenotyping, combined with analytical approaches to distinguish between selective infection and receptor modulation by viruses, can be used as a discovery tool.
