Mazzuca Pietro, Caruso Arnaldo, Caccuri Francesca
Department of Molecular and Translational Medicine, Section of Microbiology, University of Brescia Medical School, Brescia, Italy.
New Microbiol. 2016 Jul;39(3):163-173.
HIV-1 promotes a generalized immune activation that involves the main targets of HIV-1 infection but also cells that are not sensitive to viral infection. ECs display major dysfunctions in HIV+ patients during long-standing viral infection that persist even in the current cART era, in which new-generation drugs have reduced dysmetabolic side effects and successfully impeded viral replication. In vivo studies have failed to demonstrate the presence of replicating virus in ECs suggesting that a direct role of the virus is unlikely, and implying that the mechanism accounting for vascular dysfunction may rely on the indirect action of molecules released in the microenvironment by HIV-1-infected cells. This article reviews the current understanding of how HIV-1 infection can contribute to vascular dysfunction. In particular, we discuss the emerging role played by different HIV-1 proteins in driving inflammation and EC dysregulation, and highlight the need to target them for therapeutic benefit.
HIV-1会引发全身性免疫激活，这不仅涉及HIV-1感染的主要靶细胞，还包括对病毒感染不敏感的细胞。在内皮细胞（ECs）方面，长期病毒感染期间HIV阳性患者会出现严重功能障碍，即便在当前的抗逆转录病毒治疗（cART）时代，这种情况依然存在，尽管新一代药物已减少了代谢紊乱副作用并成功抑制了病毒复制。体内研究未能证明内皮细胞中存在复制病毒，这表明病毒不太可能直接发挥作用，意味着导致血管功能障碍的机制可能依赖于HIV-1感染细胞在微环境中释放的分子的间接作用。本文综述了目前对HIV-1感染如何导致血管功能障碍的理解。特别是，我们讨论了不同HIV-1蛋白在引发炎症和内皮细胞失调中所起的新作用，并强调针对它们进行治疗以获得益处的必要性。
