PDF(Pubmed)
Abstract：
HSV-1 hijacks the cellular vesicular secretion system and promotes the secretion of extracellular vesicles (EVs) from infected cells. This is believed to facilitate the maturation, secretion, intracellular transportation and immune evasion of the virus. Intriguingly, previous studies have shown that noninfectious EVs from HSV-1-infected cells exert antiviral effects on HSV-1 and have identified host restrictive factors, such as STING, CD63, and Sp100 packed in these lipid bilayer-enclosed vesicles. Octamer-binding transcription factor-1 (Oct-1) is shown here to be a pro-viral cargo in non-virion-containing EVs during HSV-1 infection and serves to facilitate virus dissemination. Specifically, during HSV-1 infection, the nuclear localized transcription factor Oct-1 displayed punctate cytosolic staining that frequently colocalized with VP16 and was increasingly secreted into the extracellular space. HSV-1 grown in cells bereft of Oct-1 (Oct-1 KO) was significantly less efficient at transcribing viral genes during the next round of infection. In fact, HSV-1 promoted increased exportation of Oct-1 in non-virion-containing EVs, but not the other VP16-induced complex (VIC) component HCF-1, and EV-associated Oct-1 was promptly imported into the nucleus of recipient cells to facilitate the next round of HSV-1 infection. Interestingly, we also found that EVs from HSV-1-infected cells primed cells for infection by another RNA virus, vesicular stomatitis virus. In summary, this investigation reports one of the first pro-viral host proteins packed into EVs during HSV-1 infection and underlines the heterogenetic nature and complexity of these noninfectious double-lipid particles.
摘要：
HSV-1劫持细胞囊泡分泌系统并促进细胞外囊泡（EV）从感染细胞的分泌。这被认为有助于成熟，分泌，病毒的胞内运输和免疫逃避。有趣的是，以前的研究表明，非感染性EV从HSV-1感染的细胞发挥对HSV-1的抗病毒作用，并已确定宿主限制性因素，比如STING,CD63和Sp100包装在这些脂质双层封闭的囊泡中。八聚体结合转录因子-1（Oct-1）在HSV-1感染期间显示为非含病毒体的EV中的前病毒货物，并有助于病毒传播。具体来说,在HSV-1感染期间，核定位转录因子Oct-1显示点状胞浆染色,常与VP16共定位,并逐渐分泌到细胞外间隙.在下一轮感染期间，在失去Oct-1（Oct-1KO）的细胞中生长的HSV-1在转录病毒基因方面的效率明显较低。事实上,HSV-1促进了不含病毒体的电动汽车中Oct-1的出口增加，而不是其他VP16诱导的复合物（VIC）成分HCF-1，并且与EV相关的Oct-1被迅速导入受体细胞的细胞核，以促进下一轮HSV-1感染。有趣的是,我们还发现，来自HSV-1感染细胞的EV使细胞被另一种RNA病毒感染，水疱性口炎病毒.总之,这项研究报告了在HSV-1感染期间包装在EVs中的首批前病毒宿主蛋白之一,并强调了这些非感染性双脂颗粒的异质性和复杂性.
