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

IFITM1 靶向 HIV-1 潜伏感染细胞,实现抗体依赖性细胞溶解

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作者: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

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.

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