Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
J Immunol. 2012 Jul 15;189(2):744-54. doi: 10.4049/jimmunol.1102244. Epub 2012 Jun 18.
Exosomes and microvesicles (MV) are cell membranous sacs originating from multivesicular bodies and plasma membranes that facilitate long-distance intercellular communications. Their functional biology, however, remains incompletely understood. Macrophage exosomes and MV isolated by immunoaffinity and sucrose cushion centrifugation were characterized by morphologic, biochemical, and molecular assays. Lipidomic, proteomic, and cell biologic approaches uncovered novel processes by which exosomes and MV facilitate HIV-1 infection and dissemination. HIV-1 was "entrapped" in exosome aggregates. Robust HIV-1 replication followed infection with exosome-enhanced fractions isolated from infected cell supernatants. MV- and exosome-facilitated viral infections are affected by a range of cell surface receptors and adhesion proteins. HIV-1 containing exosomes readily completed its life cycle in human monocyte-derived macrophages but not in CD4(-) cells. The data support a significant role for exosomes as facilitators of viral infection.
外泌体和微泡 (MV) 是源自多泡体和质膜的细胞膜囊泡,可促进细胞间的远距离通讯。然而,其功能生物学仍不完全清楚。通过免疫亲和和蔗糖垫离心分离的巨噬细胞外泌体和 MV 通过形态学、生化和分子检测进行了表征。脂质组学、蛋白质组学和细胞生物学方法揭示了外泌体和 MV 促进 HIV-1 感染和传播的新过程。HIV-1 被“捕获”在外泌体聚集体中。用从感染细胞上清液中分离的外泌体增强部分感染后,出现了强大的 HIV-1 复制。MV 和外泌体促进的病毒感染受一系列细胞表面受体和粘附蛋白的影响。含 HIV-1 的外泌体可在人单核细胞衍生的巨噬细胞中完成其生命周期,但不能在 CD4(-)细胞中完成。这些数据支持外泌体作为病毒感染促进剂的重要作用。