Lung macrophage scavenger receptor SR-A6 (MARCO) is an adenovirus type-specific virus entry receptor.
Lung macrophage scavenger receptor SR-A6 (MARCO) is an adenovirus type-specific virus entry receptor.
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DOI：
10.1371/journal.ppat.1006914
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发表时间：
2018-03
期刊：
影响因子：
6.7
通讯作者：
Greber UF
中科院分区：
文献类型：
--
作者：
Stichling N;Suomalainen M;Flatt JW;Schmid M;Pacesa M;Hemmi S;Jungraithmayr W;Maler MD;Freudenberg MA;Plückthun A;May T;Köster M;Fejer G;Greber UF
巨噬细胞是一组不同的吞噬细胞，作用于宿主保护免受应激、损伤和病原体。在这里，我们表明，清道夫受体SR-A6是人腺病毒在小鼠肺泡巨噬细胞样MPI细胞的入口受体，并为生产I型干扰素的重要。清道夫受体有助于清除内源性蛋白质、脂蛋白和病原体。MPI细胞中SR-A6的敲除、抗SR-A6抗体或可溶性细胞外SR-A6结构域降低了C5型腺病毒（HAdV-C5）结合和转导。鼠SR-A6和较低程度的人SR-A6的表达促进病毒体与人细胞的结合和转导。通过可溶性SR-A6的病毒粒子聚集和与SR-A6在MPI细胞上的邻近定位表明腺病毒与SR-A6直接相互作用。六邻体的带负电荷的高变区1（HVR 1）的缺失减少了HAdV-C5的结合和转导，这意味着SR-A6的病毒配体是六邻体。SR-A6促进HAdV-B35和HAdV-D26（两种用于造血细胞转导和人类疫苗接种的重要载体）进入巨噬细胞。这项研究强调了清道夫受体在对抗人类病毒的先天免疫中的重要性。巨噬细胞是一组不同的吞噬细胞，作用于宿主保护免受应激、损伤和病原体。它们在表型和功能上适应其局部环境，例如，腹膜巨噬细胞不同于脑驻留的小胶质细胞，不同于肝脏驻留的枯否细胞或肺中的肺巨噬细胞。气道巨噬细胞是最早接触人类呼吸道病毒（如腺病毒）的细胞之一。它们释放促炎细胞因子，杀死病原体，呈递抗原，并恢复组织。然而，病毒与肺巨噬细胞的相互作用知之甚少，也不清楚它们如何导致感染或病毒清除。在这里，我们确定了鼠清道夫受体SR-A6作为一个人腺病毒的肺泡巨噬细胞样细胞，所谓的MPI细胞的一个子集的受体。清道夫受体包括跨膜蛋白的大家族，并且有助于内源性蛋白质、脂蛋白和病原体的清除。在一系列强有力的实验中，我们表明腺病毒使用SR-A6作为MPI细胞感染和I型干扰素生产的进入受体。MPI细胞是来自胎鼠肝脏的非转化的自我更新巨噬细胞，与成人肺泡巨噬细胞非常相似。结果表明，SR-A6结合肺泡巨噬细胞样细胞表面的病毒粒子，并导致感染。
Macrophages are a diverse group of phagocytic cells acting in host protection against stress, injury, and pathogens. Here, we show that the scavenger receptor SR-A6 is an entry receptor for human adenoviruses in murine alveolar macrophage-like MPI cells, and important for production of type I interferon. Scavenger receptors contribute to the clearance of endogenous proteins, lipoproteins and pathogens. Knockout of SR-A6 in MPI cells, anti-SR-A6 antibody or the soluble extracellular SR-A6 domain reduced adenovirus type-C5 (HAdV-C5) binding and transduction. Expression of murine SR-A6, and to a lower extent human SR-A6 boosted virion binding to human cells and transduction. Virion clustering by soluble SR-A6 and proximity localization with SR-A6 on MPI cells suggested direct adenovirus interaction with SR-A6. Deletion of the negatively charged hypervariable region 1 (HVR1) of hexon reduced HAdV-C5 binding and transduction, implying that the viral ligand for SR-A6 is hexon. SR-A6 facilitated macrophage entry of HAdV-B35 and HAdV-D26, two important vectors for transduction of hematopoietic cells and human vaccination. The study highlights the importance of scavenger receptors in innate immunity against human viruses. Macrophages are a diverse group of phagocytic cells acting in host protection against stress, injury, and pathogens. They phenotypically and functionally adapt to their local environment, for example, peritoneal macrophages are distinct from brain-resident microglia, from liver-resident Kupffer cells or lung macrophages in the lung. Airway macrophages are among the first cells to encounter human respiratory viruses, such as adenoviruses. They release pro-inflammatory cytokines, kill pathogens, present antigens, and restore tissues. Yet, interactions of viruses with lung macrophages are poorly understood, and it is unclear, how they lead to infection or virus clearance. Here we identified the murine scavenger receptor SR-A6 as a receptor for a subset of human adenoviruses on alveolar macrophage-like cells, so-called MPI cells. Scavenger receptors comprise a large family of trans-membrane proteins, and contribute to the clearance of endogenous proteins, lipoproteins and pathogens. In a series of robust experimentation, we show that adenoviruses use SR-A6 as an entry receptor for infection of MPI cells, and production of type I interferon. MPI cells are non-transformed, self-renewing macrophages derived from fetal murine liver, and closely resemble adult alveolar macrophages. The results demonstrate that SR-A6 binds virions on the surface of alveolar macrophage-like cells, and leads to infection.
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DOI：
10.1038/mt.2015.194
发表时间：
2016-02
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
Alonso-Padilla J;Papp T;Kaján GL;Benkő M;Havenga M;Lemckert A;Harrach B;Baker AH
通讯作者：
Baker AH
DOI：
10.1073/pnas.1302877110
发表时间：
2013-06-11
影响因子：
11.1
作者：
Fejer, Gyoergy;Wegner, Mareike Dorothee;Freudenberg, Marina A.
通讯作者：
Freudenberg, Marina A.
影响因子：
11.4
作者：
Greber, UF;Webster, P;Helenius, A
通讯作者：
Helenius, A
影响因子：
30.3
作者：
Burckhardt, Christoph J.;Suomalainen, Maarit;Greber, Urs F.
通讯作者：
Greber, Urs F.
影响因子：
12.4
作者：
Cerullo, Vincenzo;Seiler, Michael P.;Lee, Brendan
通讯作者：
Lee, Brendan