Role of Inflammasomes in HIV-1 and Drug Abuse Mediated Neuroinflammaging

Sil, Susmita; Niu, Fang; Chivero, Ernest T.; Singh, Seema; Periyasamy, Palsamy; Buch, Shilpa

doi:10.3390/cells9081857

Cited by 20 publications

(20 citation statements)

References 216 publications

(274 reference statements)

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“…Sil et al . 51 hypothesized that HIV-1 proteins and drugs of abuse cooperatively activate inflammasomes, leading to neuroinflammation and contributing to premature aging. Glial cell activation and subsequent cerebral scarring have been noted as a hallmark of neuroinflammation in the context of HIV 52 .…”

Section: Discussionmentioning

confidence: 99%

Characterization of basal ganglia volume changes in the context of HIV and polysubstance use

Monick

Joyce

Chugh

et al. 2022

Sci Rep

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HIV and psychoactive substances can impact the integrity of the basal ganglia (BG), a neural substrate of cognition, motor control, and reward-seeking behaviors. This study assessed BG gray matter (GM) volume as a function of polysubstance (stimulant and opioid) use and HIV status. We hypothesized that comorbid polysubstance use and HIV seropositivity would alter BG GM volume differently than would polysubstance use or HIV status alone. We collected structural MRI scans, substance use history, and HIV diagnoses. Participants who had HIV (HIV +), a history of polysubstance dependence (POLY +), both, or neither completed assessments for cognition, motor function, and risk-taking behaviors (N = 93). All three clinical groups showed a left-lateralized pattern of GM reduction in the BG relative to controls. However, in the HIV + /POLY + group, stimulant use was associated with increased GM volume within the globus pallidus and putamen. This surpassed the effects from opioid use, as indicated by decreased GM volume throughout the BG in the HIV-/POLY + group. Motor learning was impaired in all three clinical groups, and in the HIV + /POLY + group, motor learning was associated with increased caudate and putamen GM volume. We also observed associations between BG GM volume and risk-taking behaviors in the HIV + /POLY- and HIV-/POLY + groups. The effects of substance use on the BG differed as a function of substance type used, HIV seropositivity, and BG subregion. Although BG volume decreased in association with HIV and opioid use, stimulants can, inversely, lead to BG volume increases within the context of HIV.

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Section: Discussionmentioning

confidence: 99%

Characterization of basal ganglia volume changes in the context of HIV and polysubstance use

Monick

Joyce

Chugh

et al. 2022

Sci Rep

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“…The high production of IL1 β in abortive HIV infection via NLRP3-mediated caspase 1 activation remarkably contributes to sustained inflammation and disease progression [ 23 ]. This sustained inflammation is important in the clinical manifestation of cardiovascular diseases [ 24 ], neurological [ 25 ], and other inflammatory diseases in HIV infection. Recently, it was shown that HIV Tat proteins trigger NLRP3 and NLRC5 inflammasome activation in microglia cells surging the production of proinflammatory cytokines that contribute to sustained neuroinflammation and bystander damage [ 25 ].…”

Section: Nlrp3 Activation In Hiv Infectionmentioning

confidence: 99%

“…This sustained inflammation is important in the clinical manifestation of cardiovascular diseases [ 24 ], neurological [ 25 ], and other inflammatory diseases in HIV infection. Recently, it was shown that HIV Tat proteins trigger NLRP3 and NLRC5 inflammasome activation in microglia cells surging the production of proinflammatory cytokines that contribute to sustained neuroinflammation and bystander damage [ 25 ]. Furthermore, HIV infects and triggers bystander damage of astrocytes and neurons in the brain via the ROS pathway and virus-induced mitochondrial damage [ 26 ].…”

Section: Nlrp3 Activation In Hiv Infectionmentioning

confidence: 99%

“…Furthermore, HIV infects and triggers bystander damage of astrocytes and neurons in the brain via the ROS pathway and virus-induced mitochondrial damage [ 26 ]. The overall neuroinflammation contributes to neuroinflammaging responsible for some of the neurodegenerative diseases associated with HIV infection [ 25 ]. Thus, by studying the P2Y2-NLRP3 interaction in early HIV infection, molecular mechanisms underlying NLRP3-mediated bystander CD4 T cell depletion, and HIV neuroinflammation new approaches for the development of HIV vaccine or therapeutic interventions can be well exploited to improve the outcome of the disease.…”

Section: Nlrp3 Activation In Hiv Infectionmentioning

confidence: 99%

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The Role of Inflammasome Activation in Early HIV Infection

Ekabe

Clinton

Kehbila

et al. 2021

Journal of Immunology Research

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The inflammasome pathway is an important arm of the innate immune system that provides antiviral immunity against many viruses. The main pathways involved in virus infections include the NLRP3, IFI16, and AIM2 pathways. However, a succinct understanding of its role in HIV is not yet well elucidated. In this review, we showed that NLRP3 inflammasome activation plays a vital role in inhibiting HIV entry into target cells via the purinergic pathway; IFI16 detects intracellular HIV ssDNA, triggers interferon I and III production, and inhibits HIV transcription; and AIM2 binds to HIV dsDNA and triggers acute inflammation and pyroptosis. Remarkably, by understanding these mechanisms, new therapeutic strategies can be developed against the disease.

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“…Drug abuse is intimately linked with HIV infection and HAND. Many drugs of abuse cause neurotoxicity and increase the susceptibility of the CNS cells to HIV infection by upregulating genes or proteins necessary for HIV transcription/replication [22][23][24][25]. Drug abuse in the context of HIV infection is extremely complicated, with many unknown variables.…”

Section: Introductionmentioning

confidence: 99%

Crossroads of Drug Abuse and HIV Infection: Neurotoxicity and CNS Reservoir

et al. 2022

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Drug abuse is a common comorbidity in people infected with HIV. HIV-infected individuals who abuse drugs are a key population who frequently experience suboptimal outcomes along the HIV continuum of care. A modest proportion of HIV-infected individuals develop HIV-associated neurocognitive issues, the severity of which further increases with drug abuse. Moreover, the tendency of the virus to go into latency in certain cellular reservoirs again complicates the elimination of HIV and HIV-associated illnesses. Antiretroviral therapy (ART) successfully decreased the overall viral load in infected people, yet it does not effectively eliminate the virus from all latent reservoirs. Although ART increased the life expectancy of infected individuals, it showed inconsistent improvement in CNS functioning, thus decreasing the quality of life. Research efforts have been dedicated to identifying common mechanisms through which HIV and drug abuse lead to neurotoxicity and CNS dysfunction. Therefore, in order to develop an effective treatment regimen to treat neurocognitive and related symptoms in HIV-infected patients, it is crucial to understand the involved mechanisms of neurotoxicity. Eventually, those mechanisms could lead the way to design and develop novel therapeutic strategies addressing both CNS HIV reservoir and illicit drug use by HIV patients.

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Role of Inflammasomes in HIV-1 and Drug Abuse Mediated Neuroinflammaging

Cited by 20 publications

References 216 publications

Characterization of basal ganglia volume changes in the context of HIV and polysubstance use

Characterization of basal ganglia volume changes in the context of HIV and polysubstance use

The Role of Inflammasome Activation in Early HIV Infection

Crossroads of Drug Abuse and HIV Infection: Neurotoxicity and CNS Reservoir

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