Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spread.
Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spread.
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DOI：
10.1186/s12977-021-00550-8
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发表时间：
2021-02-23
期刊：
影响因子：
3.3
通讯作者：
Kashanchi F
中科院分区：
文献类型：
--
作者：
Pinto DO;Al Sharif S;Mensah G;Cowen M;Khatkar P;Erickson J;Branscome H;Lattanze T;DeMarino C;Alem F;Magni R;Zhou W;Alais S;Dutartre H;El-Hage N;Mahieux R;Liotta LA;Kashanchi F
人类嗜T淋巴细胞病毒1型（HTLV - 1）是一种血源性病原体，是成人T细胞白血病/淋巴瘤（ATLL）以及HTLV - 1相关脊髓病/热带痉挛性下肢轻瘫（HAM/TSP）的病原体。目前全球已有多达1000万人感染HTLV - 1，在日本、非洲、加勒比地区和南美洲为高度流行区域。我们之前已经表明，细胞外囊泡（EVs）通过促进细胞间接触增强HTLV - 1的传播。
在此，我们使用差速超速离心（DUC）法，以2k（2000×g）、10k（10000×g）和100k（100000×g）的转速从感染细胞的上清液中将细胞外囊泡分离为亚群。蛋白质组学分析显示，在2k亚群中细胞外囊泡含有最高的病毒/宿主蛋白丰度（2k＞10k＞100k）。2k和10k亚群含有病毒蛋白（即p19和Tax）以及自噬蛋白（即LC3和p62），这表明存在自噬体以及核心组蛋白。有趣的是，在血管生成实验（间充质干细胞 + 内皮细胞）中使用2k细胞外囊泡导致类血管小管恶化。在血脑屏障（BBB）中通常与神经血管单元相关的细胞（即星形胶质细胞、神经元和巨噬细胞）表明，HTLV - 1细胞外囊泡可能诱导星形胶质细胞和单核细胞衍生的巨噬细胞中与迁移相关的细胞因子（即白细胞介素 - 8；100k＞2k＞10k和白细胞介素 - 8；2k＞10k）的表达。最后，我们发现细胞外囊泡能够促进单核细胞衍生的树突状细胞中的细胞间接触和病毒传播。在人源化小鼠模型中，2k和10k的细胞外囊泡都增加了HTLV - 1的传播，血液、淋巴结和脾脏中的前病毒DNA和RNA的增加证明了这一点。
总之，这些数据表明不同的细胞外囊泡亚群诱导细胞因子表达、组织损伤和病毒传播。
The Human T-cell Lymphotropic Virus Type-1 (HTLV-1) is a blood-borne pathogen and etiological agent of Adult T-cell Leukemia/Lymphoma (ATLL) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HTLV-1 has currently infected up to 10 million globally with highly endemic areas in Japan, Africa, the Caribbean and South America. We have previously shown that Extracellular Vesicles (EVs) enhance HTLV-1 transmission by promoting cell–cell contact. Here, we separated EVs into subpopulations using differential ultracentrifugation (DUC) at speeds of 2 k (2000×g), 10 k (10,000×g), and 100 k (100,000×g) from infected cell supernatants. Proteomic analysis revealed that EVs contain the highest viral/host protein abundance in the 2 k subpopulation (2 k > 10 k > 100 k). The 2 k and 10 k populations contained viral proteins (i.e., p19 and Tax), and autophagy proteins (i.e., LC3 and p62) suggesting presence of autophagosomes as well as core histones. Interestingly, the use of 2 k EVs in an angiogenesis assay (mesenchymal stem cells + endothelial cells) caused deterioration of vascular-like-tubules. Cells commonly associated with the neurovascular unit (i.e., astrocytes, neurons, and macrophages) in the blood–brain barrier (BBB) showed that HTLV-1 EVs may induce expression of cytokines involved in migration (i.e., IL-8; 100 k > 2 k > 10 k) from astrocytes and monocyte-derived macrophages (i.e., IL-8; 2 k > 10 k). Finally, we found that EVs were able to promote cell–cell contact and viral transmission in monocytic cell-derived dendritic cell. The EVs from both 2 k and 10 k increased HTLV-1 spread in a humanized mouse model, as evidenced by an increase in proviral DNA and RNA in the Blood, Lymph Node, and Spleen. Altogether, these data suggest that various EV subpopulations induce cytokine expression, tissue damage, and viral spread.
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影响因子：
10.6
作者：
Anderson MR;Pleet ML;Enose-Akahata Y;Erickson J;Monaco MC;Akpamagbo Y;Velluci A;Tanaka Y;Azodi S;Lepene B;Jones J;Kashanchi F;Jacobson S
通讯作者：
Jacobson S
影响因子：
4.6
作者：
Azevedo RSS;de Sousa JR;Araujo MTF;Martins Filho AJ;de Alcantara BN;Araujo FMC;Queiroz MGL;Cruz ACR;Vasconcelos BHB;Chiang JO;Martins LC;Casseb LMN;da Silva EV;Carvalho VL;Vasconcelos BCB;Rodrigues SG;Oliveira CS;Quaresma JAS;Vasconcelos PFC
通讯作者：
Vasconcelos PFC
影响因子：
5.2
作者：
Clark MC;Baum LG
通讯作者：
Baum LG
影响因子：
56.9
作者：
CLAPHAM, P;NAGY, K;WEISS, RA
通讯作者：
WEISS, RA
影响因子：
20.3
作者：
Barnard, AL;Igakura, T;Bangham, CRM
通讯作者：
Bangham, CRM