Chronic Intrahippocampal Infusion of HIV-1 Neurotoxic Proteins: A Novel Mouse Model of HIV-1 Associated Inflammation and Neural Stem Cell Dysfunction

Hill, Jeremy; Zuluaga-Ramirez, Viviana; Gajghate, Sachin; Winfield, Malika; Persidsky, Yuri

doi:10.1007/s11481-019-09846-1

Cited by 12 publications

(4 citation statements)

References 21 publications

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“…Importantly, the EcoHIV model does not fully recapitulate HIV-1 infection. One notable difference includes the absence of gp120, which is a known mediator of deleterious immune and neural outcomes in HIV-1 infection [49,94]. While consistent with general peripheral and CNS immune system dysregulation observed in rodent models of HIV [29,45,95], the time course of EcoHIV infection differs from HIV-1 [39].…”

Section: Discussionmentioning

confidence: 79%

Effects of Antiretroviral Treatment on Central and Peripheral Immune Response in Mice with EcoHIV Infection

Xie,

Namba,

Buck

et al. 2024

Cells

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HIV infection is an ongoing global health issue, despite increased access to antiretroviral therapy (ART). People living with HIV (PLWH) who are virally suppressed through ART still experience negative health outcomes, including neurocognitive impairment. It is increasingly evident that ART may act independently or in combination with HIV infection to alter the immune state, though this is difficult to disentangle in the clinical population. Thus, these experiments used multiplexed chemokine/cytokine arrays to assess peripheral (plasma) and brain (nucleus accumbens; NAc) expression of immune targets in the presence and absence of ART treatment in the EcoHIV mouse model. The findings identify the effects of EcoHIV infection and of treatment with bictegravir (B), emtricitabine (F), and tenofovir alafenamide (TAF) on the expression of numerous immune targets. In the NAc, this included EcoHIV-induced increases in IL-1α and IL-13 expression and B/F/TAF-induced reductions in KC/CXCL1. In the periphery, EcoHIV suppressed IL-6 and LIF expression, while B/F/TAF reduced IL-12p40 expression. In the absence of ART, IBA-1 expression was negatively correlated with CX3CL1 expression in the NAc of EcoHIV-infected mice. These findings identify distinct effects of ART and EcoHIV infection on peripheral and central immune factors and emphasize the need to consider ART effects on neural and immune outcomes.

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Section: Discussionmentioning

confidence: 79%

Effects of Antiretroviral Treatment on Central and Peripheral Immune Response in Mice with EcoHIV Infection

Xie,

Namba,

Buck

et al. 2024

Cells

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“…The hippocampus is essential for normal learning and memory processes, including extinction of cocaine conditioned place preference (Hitchcock and Lattal, 2018), which was impaired in HIV-1 infected mice. These ndings suggest a different pro le of hippocampal microglia response to systemic HIV-1 infection when compared to local infusion of HIV-1 proteins to the hippocampus, which induces microglial activation (Hill et al, 2019). This may re ect higher exposure to HIV-1 proteins resulting from this local infusion to the tissue.…”

Section: Discussionmentioning

confidence: 87%

Impaired extinction of cocaine seeking in HIV-infected mice is accompanied by peripheral and central immune dysregulation

Barker,

Buck,

Xie

et al. 2023

Preprint

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Substance use disorders (SUDs) are highly comorbid with HIV infection, necessitating an understanding of the interactive effects of drug exposure and HIV. The relationship between HIV infection and cocaine use disorder is likely bidirectional, with cocaine use directly impacting immune function while HIV infection alters addiction-related behavior. To better characterize the neurobehavioral and immune consequences of HIV infection and cocaine exposure, this study utilized a humanized mouse model to investigate the outcomes of HIV-1 infection on cocaine-related behaviors in a conditioned place preference (CPP) model, and the interactive effects of cocaine and HIV infection on peripheral and central nervous system inflammation. HIV infection selectively impaired cocaine CPP extinction without effecting reinstatement or cocaine seeking under conflict were observed. Behavioral alterations were accompanied by immune changes in HIV infected mice, including increased prefrontal cortex astrocyte immunoreactivity and brain-region specific effects on microglia number and reactivity. Peripheral immune system changes were observed in both mouse and human cytokines, including HIV-induced reductions in mouse IL-1α and G-CSF and human TNFα, and cocaine induced alterations in mouse GM-CSF. Together these data provide new insights into the unique neurobehavioral outcomes of HIV infection and cocaine exposure and how they interact to effect immune responses.

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“…Importantly, the EcoHIV model does not fully recapitulate HIV-1 infection. One notable difference includes the absence of gp120, which is a known mediator of deleterious immune and neural outcomes in HIV-1 infection (Gemma et al, 2000; Hill et al, 2019). While consistent with general peripheral and CNS immune system dysregulation observed in rodent models of HIV (Fitting et al, 2013; Melendez et al, 2016; Namba et al, 2023a), the time course of EcoHIV infection differs from HIV-1 (Gu et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Effects of antiretroviral treatment on central and peripheral immune response in mice with EcoHIV infection

Xie,

Namba,

Buck

et al. 2024

Preprint

View full text Add to dashboard Cite

HIV infection is an ongoing global health issue despite increased access to antiretroviral therapy (ART). People living with HIV (PLWH) who are virally suppressed through ART still experience negative health outcomes, including neurocognitive impairment. It is increasingly evident that ART may act independently or in combination with HIV infection to alter immune state, though this is difficult to disentangle in the clinical population. Thus, these experiments used multiplexed chemokine/cytokine arrays to assess peripheral (plasma) and brain (nucleus accumbens; NAc) expression of immune targets in the presence and absence of ART treatment in the EcoHIV mouse model. The findings identify effects of EcoHIV infection and of treatment with bictegravir (B), emtricitabine (F) and tenofovir alafenamide (TAF) on expression of numerous immune targets. In the NAc, this included EcoHIV-induced increases in IL-1α and IL-13 expression and B/F/TAF-induced reductions in KC/CXCL1. In the periphery, EcoHIV suppressed IL-6 and LIF expression, while B/F/TAF reduced IL-12p40 expression. In absence of ART, IBA-1 expression was negatively correlated with CX3CL1 expression in the NAc of EcoHIV-infected mice. These findings identify distinct effects of ART and EcoHIV infection on peripheral and central immune factors and emphasize the need to consider ART effects on neural and immune outcomes.

show abstract

Chronic Intrahippocampal Infusion of HIV-1 Neurotoxic Proteins: A Novel Mouse Model of HIV-1 Associated Inflammation and Neural Stem Cell Dysfunction

Cited by 12 publications

References 21 publications

Effects of Antiretroviral Treatment on Central and Peripheral Immune Response in Mice with EcoHIV Infection

Effects of Antiretroviral Treatment on Central and Peripheral Immune Response in Mice with EcoHIV Infection

Impaired extinction of cocaine seeking in HIV-infected mice is accompanied by peripheral and central immune dysregulation

Effects of antiretroviral treatment on central and peripheral immune response in mice with EcoHIV infection

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