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IFITM1 targets HIV-1 latently infected cells for antibody-dependent cytolysis
Rui André Saraiva Raposo, Miguel de Mulder Rougvie, Dominic Paquin-Proulx, Phillip M. Brailey, Vinicius D. Cabido, Paul M. Zdinak, Allison S. Thomas, Szu-han Huang, Greta A. Beckerle, Richard B. Jones, Douglas F. Nixon
Rui André Saraiva Raposo, Miguel de Mulder Rougvie, Dominic Paquin-Proulx, Phillip M. Brailey, Vinicius D. Cabido, Paul M. Zdinak, Allison S. Thomas, Szu-han Huang, Greta A. Beckerle, Richard B. Jones, Douglas F. Nixon
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Research Article AIDS/HIV Immunology

IFITM1 targets HIV-1 latently infected cells for antibody-dependent cytolysis

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Abstract

HIV-1 persistence in latent reservoirs during antiretroviral therapy (ART) is the main obstacle to virus eradication. To date, there is no marker that adequately identifies latently infected CD4+ T cells in vivo. Using a well-established ex vivo model, we generated latently infected CD4+ T cells and identified interferon-induced transmembrane protein 1 (IFITM1), a transmembrane antiviral factor, as being overexpressed in latently infected cells. By targeting IFITM1, we showed the efficient and specific killing of a latently infected cell line and CD4+ T cells from ART-suppressed patients through antibody-dependent cytolysis. We hypothesize that IFITM1 could mark natural reservoirs, identifying an immune target for killing of latently infected cells. These novel insights could be explored to develop clinical therapeutic approaches to effectively eradicate HIV-1.

Authors

Rui André Saraiva Raposo, Miguel de Mulder Rougvie, Dominic Paquin-Proulx, Phillip M. Brailey, Vinicius D. Cabido, Paul M. Zdinak, Allison S. Thomas, Szu-han Huang, Greta A. Beckerle, Richard B. Jones, Douglas F. Nixon

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Figure 3

ADCC of IFITM1+CD4+ T cells from ART-suppressed patients.

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ADCC of IFITM1+CD4+ T cells from ART-suppressed patients.
(A) Expression...
(A) Expression of IFITM1 in CD4+ T cell subsets from healthy (n = 6) and ART-suppressed patients (n = 6). Naive, stem central memory (TSCM), central memory (TCM), transitional memory (TTM), and effector memory (TEM). (B) Purified CD4+ T cells from ART-suppressed patients were incubated with anti-IFITM1 or isotype control prior to the addition of autologous effector cells at an E/T ratio of 10:1. Target cell apoptosis was detected using the FLICA assay and a live/dead marker (n = 6). (C) Cells were washed and stained with anti-CD3, -CD56, -CD107a, and –IFN-γ to detect NK cell degranulation and production of intracellular IFN-γ. Overall percentage of IFN-γ+CD107a+ NK cells in autologous or heterologous conditions (n = 6). Data are plotted as mean ± SD, and significance was determined using a nonparametric 2-tailed t test. *P < 0.05.

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