Follicular regulatory T cells are highly permissive to R5-tropic HIV-1

Shannon M. Miller, Brodie Miles, Kejun Guo, Joy Folkvord, Amie L. Meditz, Martin D. McCarter, David N. Levy, Samantha MaWhinney, Mario L. Santiago, Elizabeth Connick

Research output: Contribution to journalArticle

Abstract

Follicular regulatory T (TFR) cells are a subset of CD4+ T cells in secondary lymphoid follicles. TFR cells were previously included in the follicular helper T (TFH) cell subset, which consists of cells that are highly permissive to HIV-1. The permissivity of TFR cells to HIV-1 is unknown. We find that TFR cells are more permissive than TFH cells to R5-tropic HIV-1 ex vivo. TFR cells expressed more CCR5 and CD4 and supported higher frequencies of viral fusion. Differences in Ki67 expression correlated with HIV-1 replication. Inhibiting cellular proliferation reduced Ki67 expression and HIV-1 replication. Lymph node cells from untreated HIV-infected individuals revealed that TFR cells harbored the highest concentrations of HIV-1 RNA and highest levels of Ki67 expression. These data demonstrate that TFR cells are highly permissive to R5-tropic HIV-1 both ex vivo and in vivo. This is likely related to elevated CCR5 levels combined with a heightened proliferative state and suggests that TFR cells contribute to persistent R5-tropic HIV-1 replication in vivo.

Original languageEnglish (US)
Article numbere00430-17
JournalJournal of virology
Volume91
Issue number17
DOIs
StatePublished - Sep 1 2017

Keywords

  • Follicular helper T cell
  • Follicular regulatory T cell
  • HIV pathogenesis
  • HIV replication
  • Secondary lymphoid follicle

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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  • Cite this

    Miller, S. M., Miles, B., Guo, K., Folkvord, J., Meditz, A. L., McCarter, M. D., Levy, D. N., MaWhinney, S., Santiago, M. L., & Connick, E. (2017). Follicular regulatory T cells are highly permissive to R5-tropic HIV-1. Journal of virology, 91(17), [e00430-17]. https://doi.org/10.1128/JVI.00430-17