Madison Marisa N, Roller Richard J, Okeoma Chioma M
Department of Microbiology, Carver College of Medicine, University of Iowa, 51 Newton Road, Iowa City, IA 52242-1109, USA.
Interdisciplinary Program in Molecular and Cellular Biology, University of Iowa, Iowa City, IA 52242, USA.
Retrovirology. 2014 Nov 19;11:102. doi: 10.1186/s12977-014-0102-z.
Exosomes are membranous nanovesicles secreted into the extracellular milieu by diverse cell types. Exosomes facilitate intercellular communication, modulate cellular pheno/genotype, and regulate microbial pathogenesis. Although human semen contains exosomes, their role in regulating infection with viruses that are sexually transmitted remains unknown. In this study, we used semen exosomes purified from healthy human donors to evaluate the role of exosomes on the infectivity of different strains of HIV-1 in a variety of cell lines.
We show that human semen contains a heterologous population of exosomes, enriched in mRNA encoding tetraspanin exosomal markers and various antiviral factors. Semen exosomes are internalized by recipient cells and upon internalization, inhibit replication of a broad array of HIV-1 strains. Remarkably, the anti-HIV-1 activity of semen exosomes is specific to retroviruses because semen exosomes blocked replication of the murine AIDS (mAIDS) virus complex (LP-BM5). However, exosomes from blood had no effect on HIV-1 or LP-BM5 replication. Additionally, semen and blood exosomes had no effect on replication of herpes simplex virus; types 1 and 2 (HSV1 and HSV2). Mechanistic studies indicate that semen exosomes exert a post-entry block on HIV-1 replication by orchestrating deleterious effects on particle-associated reverse transcriptase activity and infectivity.
These illuminating findings i) improve our knowledge of the cargo of semen exosomes, ii) reveal that semen exosomes possess anti-retroviral activity, and iii) suggest that semen exosome-mediated inhibition of HIV-1 replication may provide novel opportunities for the development of new therapeutics for HIV-1.
外泌体是由多种细胞类型分泌到细胞外环境中的膜性纳米囊泡。外泌体促进细胞间通讯，调节细胞表型/基因型，并调节微生物发病机制。尽管人类精液中含有外泌体，但其在调节性传播病毒感染中的作用尚不清楚。在本研究中，我们使用从健康人类供体中纯化的精液外泌体来评估外泌体对多种细胞系中不同HIV-1毒株感染性的作用。
我们发现人类精液含有异质性的外泌体群体，富含编码四跨膜蛋白外泌体标志物和各种抗病毒因子的mRNA。精液外泌体被受体细胞内化，内化后可抑制多种HIV-1毒株的复制。值得注意的是，精液外泌体的抗HIV-1活性对逆转录病毒具有特异性，因为精液外泌体可阻断鼠类艾滋病（mAIDS）病毒复合物（LP-BM5）的复制。然而，血液来源的外泌体对HIV-1或LP-BM5的复制没有影响。此外，精液和血液来源的外泌体对单纯疱疹病毒1型和2型（HSV1和HSV2）的复制也没有影响。机制研究表明，精液外泌体通过对颗粒相关逆转录酶活性和感染性产生有害影响，对HIV-1复制发挥进入后阻断作用。
这些有启发性的发现：i）增进了我们对精液外泌体所载物质的了解；ii）揭示精液外泌体具有抗逆转录病毒活性；iii）表明精液外泌体介导的HIV-1复制抑制可能为开发HIV-1新疗法提供新机会。
