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Cell Rep. 2017 Jul 25;20(4):984-998. doi: 10.1016/j.celrep.2017.06.087.

Mass Cytometric Analysis of HIV Entry, Replication, and Remodeling in Tissue CD4+ T Cells.

Author information

1
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
2
Department of Data Sciences and Operations, University of Southern California, Los Angeles, CA 90089, USA.
3
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA.
4
Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
5
Department of Microbiology and Immunology and the Helen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115, USA.
6
Department of Pathology, Stanford School of Medicine, Stanford, CA 94305-5324, USA; Palo Alto Veterans Institute for Research and the Palo Alto Veterans Affairs Health Care Center, Palo Alto, CA 94304-1290, USA.
7
Department of Medicine, University of Alabama, Birmingham, AL 35233-1912, USA.
8
Department of Medicine, University of Alabama, Birmingham, AL 35233-1912, USA; Center for AIDS Research, University of Alabama, Birmingham, AL 35294-2107, USA.
9
Departments of Pediatrics and Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5324, USA.
10
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
11
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA; Department of Urology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: nadia.roan@ucsf.edu.

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.

KEYWORDS:

CD127; CD4+ T cell; CyTOF; HIV; remodeling; viral fusion

PMID:
28746881
PMCID:
PMC5560086
DOI:
10.1016/j.celrep.2017.06.087
[Indexed for MEDLINE]
Free PMC Article

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