The Role of Pannexin-1 Channels in HIV and NeuroHIV Pathogenesis

Abstract

The human immunodeficiency virus-1 (HIV) enters the brain shortly after infection, leading to long-term neurological complications in half of the HIV-infected population, even in the current anti-retroviral therapy (ART) era. Despite decades of research, no biomarkers can objectively measure and, more importantly, predict the onset of HIV-associated neurocognitive disorders. Several biomarkers have been proposed; however, most of them only reflect late events of neuronal damage. Our laboratory recently identified that ATP and PGE2, inflammatory molecules released through Pannexin-1 channels, are elevated in the serum of HIV-infected individuals compared to uninfected individuals and other inflammatory diseases. More importantly, high circulating ATP levels, but not PGE2, can predict a decline in cognition, suggesting that HIV-infected individuals have impaired ATP metabolism and associated signaling. We identified that Pannexin-1 channel opening contributes to the high serological ATP levels, and ATP in the circulation could be used as a biomarker of HIV-associated cognitive impairment. In addition, we believe that ATP is a major contributor to chronic inflammation in the HIV-infected population, even in the anti-retroviral era. Here, we discuss the mechanisms associated with Pannexin-1 channel opening within the circulation, as well as within the resident viral reservoirs, ATP dysregulation, and cognitive disease observed in the HIV-infected population.

Influence of the Gut Microbiota on the Development of Neurodegenerative Diseases

“…Formerly, NO is recognized as a potential relaxing factor derived from the endothelium and is abbreviated as EDRF. Therefore, it mediates the relaxation of a variety of blood vessels [ 67 ].…”

Mechanisms of HIV-mediated blood-brain barrier compromise and leukocyte transmigration under the current antiretroviral era

“…However, during pathological conditions or certain cell functions such as chemokine signaling, T cell differentiation, and apoptosis, the Panx-1 channel opens and releases cytoplasmic inflammatory molecules such as ATP, which signals through purinergic receptors. 10 Panx-1 inhibition prevents synaptic and neuronal compromise within the brains of SIV-infected macaques, demonstrating that Panx-1 opening plays a critical role in HAND pathogenesis. 11 However, all these data were obtained during acute infection; thus, how eATP in chronic conditions can predict or contribute to cognitive impairment is unknown.…”