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病毒再激活后 CD20 的表达使 HIV 储存细胞对利妥昔单抗敏感。

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

机构信息

Infectious Disease Department, Hospital Universitari Vall d'Hebrón, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.

Infectious Disease Department, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.

出版信息

Nat Commun. 2019 Aug 16;10(1):3705. doi: 10.1038/s41467-019-11556-4.

DOI:10.1038/s41467-019-11556-4
PMID:31420544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6697690/
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.

摘要

鉴定专门针对 HIV 储存细胞的标志物将是寻找治愈 HIV 疗法的重大进展。在这里，我们确定 B 淋巴细胞抗原 CD20 是体外和体内感染 HIV 细胞的标志物。CD20 分子在血液中 CD4 阳性（CD4）T 淋巴细胞的一个亚群中表达不明显，这些细胞具有高水平的细胞激活和异质记忆表型。在感染患者的淋巴结样本中，CD20 存在于具有感染力的 HIV 感染细胞中，体外病毒感染在早期感染期间选择性地上调 CD20 的表达。在接受抗逆转录病毒治疗（ART）的患者样本中，这个亚群中 HIV 转录本明显富集，抗 CD20 单克隆抗体利妥昔单抗诱导细胞杀伤，当与潜伏逆转剂联合使用时，可减少表达 HIV 的细胞池。我们为在接受 ART 的患者病毒重新激活后靶向这个活跃的 HIV 储存库提供了一种工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/3623336467ba/41467_2019_11556_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/ba3f7b755e86/41467_2019_11556_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/4bdc33b17cee/41467_2019_11556_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/50bf9064292e/41467_2019_11556_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/6452c55bf9f0/41467_2019_11556_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/11d3e7094c92/41467_2019_11556_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/9f1967d8b7c8/41467_2019_11556_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/960bf83ee905/41467_2019_11556_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/3623336467ba/41467_2019_11556_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/ba3f7b755e86/41467_2019_11556_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/4bdc33b17cee/41467_2019_11556_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/50bf9064292e/41467_2019_11556_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/6452c55bf9f0/41467_2019_11556_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/11d3e7094c92/41467_2019_11556_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/9f1967d8b7c8/41467_2019_11556_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/960bf83ee905/41467_2019_11556_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c238/6697690/3623336467ba/41467_2019_11556_Fig8_HTML.jpg

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