中文摘要：
巨噬细胞在感染单纯疱疹病毒1型（HSV-1）期间具有重要的保护功能。然而，限制病毒传播并防止严重疾病的分子机制尚不清楚。在这里，我们显示巨噬细胞通过内吞作用摄取HSV-1，并将病毒颗粒运送到多泡体（MVBs）中。在MVBs中，酸性神经酰胺酶（aCDase）将神经酰胺转化为鞘氨醇，并增加富含鞘氨醇的内腔囊泡（ILVs）的形成。一旦HSV-1颗粒到达MVBs，富含鞘氨醇的ILVs会与HSV-1颗粒结合，从而限制其与限制性内体膜的融合，并阻止细胞感染。在巨噬细胞培养中缺乏aCDase或在Asah1−/− 小鼠中会导致HSV-1的复制，Asah1−/− 小鼠在全身或阴道内接种后很快死亡。对巨噬细胞进行增强鞘氨醇的化合物处理可阻止HSV-1的传播，提示该途径具有潜在的治疗价值。总之，aCDase将ILVs加载鞘氨醇，从而阻止HSV-1衣壳进入胞质。
英文摘要：
Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1−/− mice results in replication of HSV-1 and Asah1−/− mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids from penetrating into the cytosol.
论文信息：
论文题目：Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease
期刊名称：Nature Communications
时间期卷：11, Article number: 1338(2020)
在线时间：2020年3月12日
DOI： doi.org/10.1038/s41467-020-15072-8
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes& Control Liposomes
办事处：Target Technology(靶点科技)
Clodronate Liposomes氯膦酸盐脂质体清除病毒模型中巨噬细胞 ，荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Nature Communications：巨噬细胞的酸性神经酰胺酶将单纯疱疹病毒困在多囊泡体中，并防止严重疾病。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除肿瘤相关巨噬细胞的材料和方法：
D-erythro-sphingosine (C18, 860490) and D-Galactosyl-β1-1’-N-Nervonoyl-D-erythro-sphingosine (C24:1, β-D-Galactosyl Ceramide, 110759), were obtained from Avanti Polar Lipids (Alabaster, AL, USA). Glycoceramidase (E9030-100MUN), sphingomyelinase (S8633-25UN), Cy3-linked DBCO (777366-1 mg) and DAPI (D9542) were purchased from Millipore Sigma (Darmstadt, Germany). Recombinant mouse Asah2 (3558-AH) was purchased from R&D Systems (Minneapolis, MN, USA). The sphingosine kinase inhibitor SKI-II (CAS # 312636-16-1; Cat # 2097) was obtained from Tocris Bioscience (Bristol, United Kingdom) and tamoxifen (CAS # 10540-29-1, Cat # T5648-5G) and cornoil (CAS # 8001-30-7, Cat # C8267-500ML) from Millipore Sigma. Clodronate and control liposomes were purchased from Liposoma (CP-005-005, Amsterdam, Netherlands). Clickable ω-azido-sphingosine ((2S,3R,E)-2-amino-18-azidooctadec-4-ene-1,3-diol) for click chemistry42 staining was synthesized in-house by Julian Fink.
Depletion of macrophages
For macrophage-depleted mouse experiments, mice were treated intravenously with 50 mg/kg clodronate to deplete tissue resident macrophages. After 3 days, mice were ready to be used in experiments.
材料和方法文献截图：
