The Wistar Institute, Philadelphia, PA, USA.
Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA.
Methods Mol Biol. 2022;2442:463-474. doi: 10.1007/978-1-0716-2055-7_25.
The β-galactoside-binding protein Galectin-9 (Gal-9) functions as a double-edged sword during HIV infection. On the one hand, Gal-9 can reactivate HIV latently infected cells, the main barrier to achieving HIV eradication, making them visible to immune clearance. On the other hand, Gal-9 induces latent HIV transcription by activating T cell Receptor (TCR) signaling pathways. These signaling pathways induce undesirable pro-inflammatory responses. While these unwanted responses can be mitigated by rapamycin without impacting Gal-9-mediated latent HIV reactivation, this effect raises the concern that Gal-9 may play a role in the chronic immune activation/inflammation that persists in people living with HIV despite antiretroviral therapy. Together, these data highlight the need to understand the positive and negative impacts of galectin interactions on immunological functions during HIV infection. In this chapter, we describe methods that can be used to investigate the effects of galectins, in particular Gal-9, on latent HIV transcription in vitro and ex vivo.
β-半乳糖苷结合蛋白 Galectin-9(Gal-9)在 HIV 感染过程中发挥双刃剑作用。一方面,Gal-9 可以重新激活 HIV 潜伏感染的细胞,这是实现 HIV 根除的主要障碍,使它们能够被免疫清除。另一方面,Gal-9 通过激活 T 细胞受体(TCR)信号通路诱导潜伏 HIV 的转录。这些信号通路诱导不受欢迎的促炎反应。虽然 rapamycin 可以减轻这些不需要的反应,而不影响 Gal-9 介导的潜伏 HIV 重新激活,但这一效果引起了人们的关注,即 Gal-9 可能在抗逆转录病毒治疗后仍持续存在于 HIV 感染者中的慢性免疫激活/炎症中发挥作用。总之,这些数据强调了需要了解 Galectin 相互作用在 HIV 感染期间对免疫功能的积极和消极影响。在本章中,我们描述了可用于研究 Galectin,特别是 Gal-9,对体外和体内潜伏 HIV 转录的影响的方法。