Mass Cytometric Analysis of HIV Entry, Replication, and Remodeling in Tissue CD4+ T Cells
Marielle Cavrois,
Trambak Banerjee,
Gourab Mukherjee,
Nandhini Raman,
Rajaa Hussien,
Brandon Aguilar Rodriguez,
Joshua Vasquez,
Matthew H. Spitzer,
Nicole H. Lazarus,
Jennifer J. Jones,
Christina Ochsenbauer,
Joseph M. McCune,
Eugene C. Butcher,
Ann M. Arvin,
Nandini Sen,
Warner C. Greene,
Nadia R. Roan
Affiliations
Marielle Cavrois
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
Trambak Banerjee
Department of Data Sciences and Operations, University of Southern California, Los Angeles, CA 90089, USA
Gourab Mukherjee
Department of Data Sciences and Operations, University of Southern California, Los Angeles, CA 90089, USA
Nandhini Raman
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
Rajaa Hussien
Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA
Brandon Aguilar Rodriguez
Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA
Joshua Vasquez
Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA
Matthew H. Spitzer
Department of Microbiology and Immunology and the Helen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115, USA
Nicole H. Lazarus
Department of Pathology, Stanford School of Medicine, Stanford, CA 94305-5324, USA
Jennifer J. Jones
Department of Medicine, University of Alabama, Birmingham, AL 35233-1912, USA
Christina Ochsenbauer
Department of Medicine, University of Alabama, Birmingham, AL 35233-1912, USA
Joseph M. McCune
Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA
Eugene C. Butcher
Department of Pathology, Stanford School of Medicine, Stanford, CA 94305-5324, USA
Ann M. Arvin
Departments of Pediatrics and Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5324, USA
Nandini Sen
Departments of Pediatrics and Microbiology and Immunology, Stanford School of Medicine, Stanford, CA 94305-5324, USA
Warner C. Greene
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
Nadia R. Roan
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
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.
