Expression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to Rituximab

病毒再激活后CD20的表达使HIV储存细胞对利妥昔单抗敏感

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作者:Carla Serra-Peinado ,Judith Grau-Expósito ,Laura Luque-Ballesteros ,Antonio Astorga-Gamaza ,Jordi Navarro ,Jenny Gallego-Rodriguez ,Mario Martin ,Adrià Curran ,Joaquin Burgos ,Esteban Ribera ,Berta Raventós ,Rein Willekens ,Ariadna Torrella ,Bibiana Planas ,Rosa Badía ,Felipe Garcia ,Josep Castellví ,Meritxell Genescà ,Vicenç Falcó ,Maria J Buzon

Abstract

The identification of exclusive markers to target HIV-reservoir cells will represent a significant advance in the search for therapies to cure HIV. Here, we identify the B lymphocyte antigen CD20 as a marker for HIV-infected cells in vitro and in vivo. The CD20 molecule is dimly expressed in a subpopulation of CD4-positive (CD4+) T lymphocytes from blood, with high levels of cell activation and heterogeneous memory phenotypes. In lymph node samples from infected patients, CD20 is present in productively HIV-infected cells, and ex vivo viral infection selectively upregulates the expression of CD20 during early infection. In samples from patients on antiretroviral therapy (ART) this subpopulation is significantly enriched in HIV transcripts, and the anti-CD20 monoclonal antibody Rituximab induces cell killing, which reduces the pool of HIV-expressing cells when combined with latency reversal agents. We provide a tool for targeting this active HIV-reservoir after viral reactivation in patients while on ART.

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