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

Guorui Xie; Xiaoyu Luo; Tongcui Ma; Julie Frouard; Jason Neidleman; Rebecca Hoh; Steven G Deeks; Warner C Greene; Nadia R Roan

doi:10.1016/j.celrep.2021.109038

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

Cell Rep. 2021 Apr 27;35(4):109038. doi: 10.1016/j.celrep.2021.109038.

Authors

Guorui Xie¹, Xiaoyu Luo², Tongcui Ma¹, Julie Frouard¹, Jason Neidleman¹, Rebecca Hoh³, Steven G Deeks⁴, Warner C Greene⁵, Nadia R Roan⁶

Affiliations

¹ Gladstone Institute of Virology, San Francisco, CA 94158, USA; Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA.
² Gladstone Institute of Virology, San Francisco, CA 94158, USA.
³ Departments of Medicine and Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
⁴ Division of HIV, Infectious Diseases and Global Medicine, University of California San Francisco, San Francisco, CA 94110, USA.
⁵ Gladstone Institute of Virology, San Francisco, CA 94158, USA; Departments of Medicine and Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
⁶ Gladstone Institute of Virology, San Francisco, CA 94158, USA; Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: nadia.roan@gladstone.ucsf.edu.

Abstract

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.

Keywords: CD4 T cell; CyTOF; HIV; T effector memory; T follicular helper; in vivo; viral-induced remodeling; viremic.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

CD4-Positive T-Lymphocytes / metabolism*
HIV-1 / genetics*
Humans
Immunologic Memory / genetics*
T-Lymphocyte Subsets / metabolism*

Abstract

Publication types

MeSH terms

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