Purinergic Receptors: Elucidating the Role of these Immune Mediators in HIV-1 Fusion

Freeman, Tracey; Swartz, Talia H.

doi:10.3390/v12030290

Cited by 16 publications

(9 citation statements)

References 117 publications

(180 reference statements)

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“…These immune responses directly damage the lymphoid tissue and cause immune dysfunction [ 33 , 34 ]. Together, these processes lead to immune cell senescence and increased soluble immune mediators, including CRP, IL-6, and TNF-α, which do not normalize in PWH despite being treated with ART [ 2 ], [ 3 ], [ 4 , 35 ], [ 36 ], [ 37 ]. Persistent viremia in HIV-1 targeted sites is thought to be responsible for chronic systemic inflammation widely associated with HIV-1.…”

Section: Chronic Inflammation In Hiv-1 Infectionmentioning

confidence: 99%

The impact of cannabinoids on inflammasome signaling in HIV-1 infection

Min

Keane

Weinstein

et al. 2023

NeuroImmune Pharmacology and Therapeutics

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Human immunodeficiency virus type 1 (HIV-1) is a chronic disease that afflicts over 38 million people worldwide without a known cure. The advent of effective antiretroviral therapies (ART) has significantly decreased the morbidity and mortality associated with HIV-1 infection in people living with HIV-1 (PWH), thanks to durable virologic suppression. Despite this, people with HIV-1 experience chronic inflammation associated with co-morbidities. While no single known mechanism accounts for chronic inflammation, there is significant evidence to support the role of the NLRP3 inflammasome as a key driver. Numerous studies have demonstrated therapeutic impact of cannabinoids, including exerting modulatory effects on the NLRP3 inflammasome. Given the high rates of cannabinoid use in PWH, it is of great interest to understand the intersecting biology of the role of cannabinoids in HIV-1-associated inflammasome signaling. Here we describe the literature of chronic inflammation in people with HIV, the therapeutic impact of cannabinoids in PWH, endocannabinoids in inflammation, and HIV-1-associated inflammation. We describe a key interaction between cannabinoids, the NLRP3 inflammasome, and HIV-1 viral infection, which supports further investigation of the critical role of cannabinoids in HIV-1 infection and inflammasome signaling.

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Section: Chronic Inflammation In Hiv-1 Infectionmentioning

confidence: 99%

The impact of cannabinoids on inflammasome signaling in HIV-1 infection

Min

Keane

Weinstein

et al. 2023

NeuroImmune Pharmacology and Therapeutics

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“…Another purinergic receptor antagonist, suramin, has also shown inhibitory effects on RT in vitro [ 167 ]. These effects and the ones referred to in the above paragraph regarding POM-1 are all off-target effects of the pharmacological purinergic receptor inhibitors that influence HIV [ 168 ]. Therefore, phenotypes seen by treatment with these inhibitors must be analyzed carefully and be conducted in tandem with siRNA knockdowns to ensure the phenotype is recapitulated.…”

Section: Panx-1 and Purinergic Signaling Axis In Hiv Infectionmentioning

confidence: 99%

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

Hernandez

Eugenin

2022

Cells

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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.

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“…SARS-CoV-2 Alpha, Beta and Delta variants displayed enhanced spike-mediated cell fusion with syncytia formation (153). Interestingly, P2X1-specific antagonistic compounds have implicated a role for this particular purinergic pathway in HIV-1 membrane fusion, although precise mechanisms remain uncertain (154).…”

Section: Purinergic Targets For Sars-cov-2 Induced Pathologiesmentioning

confidence: 99%

The Potential of Purinergic Signaling to Thwart Viruses Including SARS-CoV-2

2022

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A long-shared evolutionary history is congruent with the multiple roles played by purinergic signaling in viral infection, replication and host responses that can assist or hinder viral functions. An overview of the involvement of purinergic signaling among a range of viruses is compared and contrasted with what is currently understood for SARS-CoV-2. In particular, we focus on the inflammatory and antiviral responses of infected cells mediated by purinergic receptor activation. Although there is considerable variation in a patient’s response to SARS-CoV-2 infection, a principle immediate concern in Coronavirus disease (COVID-19) is the possibility of an aberrant inflammatory activation causing diffuse lung oedema and respiratory failure. We discuss the most promising potential interventions modulating purinergic signaling that may attenuate the more serious repercussions of SARS-CoV-2 infection and aspects of their implementation.

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Purinergic Receptors: Elucidating the Role of these Immune Mediators in HIV-1 Fusion

Cited by 16 publications

References 117 publications

The impact of cannabinoids on inflammasome signaling in HIV-1 infection

The impact of cannabinoids on inflammasome signaling in HIV-1 infection

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

The Potential of Purinergic Signaling to Thwart Viruses Including SARS-CoV-2

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