Extracellular Vesicles in Smoking-Mediated HIV Pathogenesis and their Potential Role in Biomarker Discovery and Therapeutic Interventions

Abstract

In the last two decades, the mortality rate in people living with HIV/AIDS (PLWHA) has decreased significantly, resulting in an almost normal longevity in this population. However, a large portion of this population still endures a poor quality of life, mostly due to an increased inclination for substance abuse, including tobacco smoking. The prevalence of smoking in PLWHA is consistently higher than in HIV negative persons. A predisposition to cigarette smoking in the setting of HIV potentially leads to exacerbated HIV replication and a higher risk for developing neurocognitive and other CNS disorders. Oxidative stress and inflammation have been identified as mechanistic pathways in smoking-mediated HIV pathogenesis and HIV-associated neuropathogenesis. Extracellular vesicles (EVs), packaged with oxidative stress and inflammatory agents, show promise in understanding the underlying mechanisms of smoking-induced HIV pathogenesis via cell-cell interactions. This review focuses on recent advances in the field of EVs with an emphasis on smoking-mediated HIV pathogenesis and HIV-associated neuropathogenesis. This review also provides an overview of the potential applications of EVs in developing novel therapeutic carriers for the treatment of HIV-infected individuals who smoke, and in the discovery of novel biomarkers that are associated with HIV-smoking interactions in the CNS.

Keywords: HIV; HIV-associated neurocognitive disorders; cigarette smoking; extracellular vesicles.

Figure 1

Basic characteristics and potential applications of extracellular vesicles upon exposure to HIV and tobacco smoke.

Figure 2

Therapeutic potential of using EVs in HIV-tobacco smoking comorbidity. siRNA: Small interfering RNA; miRNA: microRNA; MHCII: major histocompatibility complex II; L1CAM: L1 cell adhesion molecule; Aβ:Amyloid beta; Neurofilament Light; HMGB1: High mobility group box 1; IL-6: Interleukin 6; RANTES: Regulated on activation, normal T cell expressed and secreted; CD14: Cluster of differentiation14