Susceptibility of Tissue Cells to HIV

Susceptibility of Tissue Cells to HIV

Mass cytometry, or CyTOF, is a powerful technology that has been used for comprehensive multiparameter characterization of immune cells. In collaboration with Dr. Marielle Cavrois (The J. David Gladstone Institutes), we recently conducted a 38-parameter characterization of HIV entry and productive infection of tissue CD4+ T cells by CyTOF, and developed 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. These studies identified a subset of memory CD4+ T cells susceptible to HIV entry but not productive infection. Ongoing work in the lab seeks to characterize the molecular basis of this post-entry restriction, and to use CyTOF and a variety of high-dimensional CyTOF data analysis tools to characterize the types of cells that are productively and latently infected with HIV.

 Susceptibility of Tissue Cells to HIV

Schematic illustrating the steps involved in characterizing the susceptibility of tissue-derived CD4+ T cells to HIV infection. Tonsils were processed into human lymphocyte aggregate cultures (HLACs), infected with an HIV-1 reporter virus, and then monitored for HIV entry after 2 hours or productive infection after 4 days. Using a variety of visualization, clustering, and statistical approaches, the susceptibility of different subsets of CD4+ T cells to HIV entry and productive infection was assessed, which led to the discovery of a new subset of memory CD4+ T cells highly susceptible to HIV entry but not productive infection. We are currently using these analytical approaches to characterize how HIV changes the properties of CD4+ T cells upon infection, including studies using patient cells.

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Funding sources for project:

  • NIH R01 AI127219 “Elucidating the mechanism of progesterone-induced permissivity in the upper female reproductive tract” (PI Roan)
  • amfAR 109301, as part of the amfAR Institute for HIV Cure Research
  • NIH Women’s Interagency HIV Study (WIHS)
  • UCSF Department of Urology startup funds

Selected publications related to project:

  • Roan NR, Jakobsen MR (2016) Friend or Foe: Innate sensing of HIV in the female reproductive tract. Curr HIV/AIDS Rep