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

SUMMARY 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.