IU School of Medicine, Pulmonary, Critical Care, Sleep and Occupational Medicine, Indianapolis, IN 46202, USA.
Brigham and Women's Hospital, Department of Medicine, Boston, MA 02115, USA.
Viruses. 2021 Jun 18;13(6):1168. doi: 10.3390/v13061168.
This article reviews the current knowledge on how viruses may utilize Extracellular Vesicle Assisted Inflammatory Load (EVAIL) to exert pathologic activities. Viruses are classically considered to exert their pathologic actions through acute or chronic infection followed by the host response. This host response causes the release of cytokines leading to vascular endothelial cell dysfunction and cardiovascular complications. However, viruses may employ an alternative pathway to soluble cytokine-induced pathologies-by initiating the release of extracellular vesicles (EVs), including exosomes. The best-understood example of this alternative pathway is human immunodeficiency virus (HIV)-elicited EVs and their propensity to harm vascular endothelial cells. Specifically, an HIV-encoded accessory protein called the "negative factor" (Nef) was demonstrated in EVs from the body fluids of HIV patients on successful combined antiretroviral therapy (ART); it was also demonstrated to be sufficient in inducing endothelial and cardiovascular dysfunction. This review will highlight HIV-Nef as an example of how HIV can produce EVs loaded with proinflammatory cargo to disseminate cardiovascular pathologies. It will further discuss whether EV production can explain SARS-CoV-2-mediated pulmonary and cardiovascular pathologies.
本文综述了病毒如何利用细胞外囊泡辅助炎症负荷（EVAIL）发挥病理作用的最新知识。病毒通常被认为通过急性或慢性感染及其宿主反应发挥其病理作用。这种宿主反应导致细胞因子的释放，导致血管内皮细胞功能障碍和心血管并发症。然而，病毒可能采用另一种途径来通过可溶性细胞因子诱导的病理——通过启动细胞外囊泡（EVs）的释放，包括外泌体。这种替代途径最被理解的例子是人类免疫缺陷病毒（HIV）引发的 EVs 及其对血管内皮细胞的损伤倾向。具体来说，在成功接受联合抗逆转录病毒治疗（ART）的 HIV 患者的体液中，从 HIV 中分离出的一种 HIV 编码辅助蛋白，即“负因子”（Nef），被证明存在于 EV 中，它也被证明足以诱导内皮和心血管功能障碍。本文将以 HIV-Nef 为例，探讨 HIV 如何产生富含促炎物质的 EV 来传播心血管疾病，并进一步讨论 EV 的产生是否可以解释 SARS-CoV-2 介导的肺部和心血管疾病。
