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Characterization of HIV-induced remodeling reveals differences in infection susceptibility of memory CD4+ T cell subsets in vivo.

  • Author(s): Xie, Guorui
  • Luo, Xiaoyu
  • Ma, Tongcui
  • Frouard, Julie
  • Neidleman, Jason
  • Hoh, Rebecca
  • Deeks, Steven G
  • Greene, Warner C
  • Roan, Nadia R
  • et al.

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Relatively little is known about features of T cells targeted by HIV in vivo. By applying bioinformatics analysis to mass cytometry (CyTOF)-phenotyped specimens from individuals with viremia and in-vitro-infected cells from uninfected donors, we provide an atlas of the phenotypes of in vivo and in vitro HIV-susceptible cells. T helper 17 (Th17) and α4β1+ cells are preferentially targeted in vivo, whereas T effector memory (Tem), T transitional memory (Ttm), Th1, and Th1/Th17 subsets are targeted in vitro. Multiple proteins-including chemokine and cytokine receptors-are remodeled by HIV in vivo, and these changes are mostly recapitulated in vitro. HIV remodels cells to a T follicular helper (Tfh) phenotype. Using clustering, we uncover a subset of CD29-expressing, Tem-like cells that are highly susceptible to infection in vivo and in vitro and experimentally confirm that susceptibility. These studies provide an in-depth look at features of HIV-susceptible cells in individuals with viremia and demonstrate that some-but not all-HIV-susceptible cells identified in vitro effectively model in vivo susceptibility.

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