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

Publication date: 25 July 2017
Source:Cell Reports, Volume 20, Issue 4
Author(s): 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
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.

Graphical abstract

Teaser

Cavrois et al. conduct a global characterization of HIV entry and productive infection of tissue CD4+ T cells by CyTOF and develop an analytical approach that takes advantage of the high-dimensional nature of CyTOF datasets to distinguish receptors modulated during infection from those differentially expressed on preferentially infected cells.


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