482 results match your criteria siv brains


HIV/SIV-infection induces opening of Pannexin-1 channels resulting in neuronal synaptic compromise: a novel therapeutic opportunity to prevent NeuroHIV.

J Neurochem 2021 Apr 26. Epub 2021 Apr 26.

Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch (UTMB), Galveston, Texas, USA.

In healthy conditions, pannexin-1 (Panx-1) channels are in a close state, but in several pathological conditions, including HIV and NeuroHIV, the channel becomes open. However, the mechanism or contribution of Panx-1 channels to the Human Immunodeficiency Virus-1 (HIV) pathogenesis and NeuroHIV are unknown. To determine the contribution of Panx-1 channels to the pathogenesis of NeuroHIV, we used a well-established model of Simian Immunodeficiency Virus (SIV) infection in macaques (Macaca mulatta) in the presence of and absence of a Panx-1 blocker to later examine the synaptic/axonal compromise induced for the virus. Read More

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ART administration reduces neuroinflammation without restoring BDNF signaling in alcohol-administered SIV-infected macaques.

AIDS 2021 Mar 31. Epub 2021 Mar 31.

Department of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA Comprehensive Alcohol-HIV/AIDS Research Center, Louisiana State University Health Sciences Center, New Orleans, LA Department of Microbiology, Immunology, and Parasitology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA Biostatistics, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA.

Objective: This study examined interactions between simian immunodeficiency virus (SIV), chronic binge alcohol (CBA), and antiretroviral therapy (ART) on growth factor signaling, neuroinflammatory markers, viral loads (VL), and CD4 counts.

Design: Adult male rhesus macaques were administered CBA (13-14 g EtOH/kg/week) or sucrose (SUC) three months prior to SIVmac251 infection until study endpoint. At viral setpoint, a subset of CBA/SIV+ and SUC/SIV+ macaques were randomized to receive daily ART (PMPA 20 mg/kg, FTC, 30 mg/kg). Read More

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Dimethyl Fumarate, an Approved Multiple Sclerosis Treatment, Reduces Brain Oxidative Stress in SIV-Infected Rhesus Macaques: Potential Therapeutic Repurposing for HIV Neuroprotection.

Antioxidants (Basel) 2021 Mar 9;10(3). Epub 2021 Mar 9.

Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Dimethyl fumarate (DMF), an antioxidant/anti-inflammatory drug approved for the treatment of multiple sclerosis, induces antioxidant enzymes, in part through transcriptional upregulation. We hypothesized that DMF administration to simian immunodeficiency virus (SIV)-infected rhesus macaques would induce antioxidant enzyme expression and reduce oxidative injury and inflammation throughout the brain. Nine SIV-infected, CD8-T-lymphocyte-depleted rhesus macaques were studied. Read More

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Chronic Opioid Administration is Associated with Prevotella-dominated Dysbiosis in SIVmac251 Infected, cART-treated Macaques.

J Neuroimmune Pharmacol 2021 Mar 31. Epub 2021 Mar 31.

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.

People living with the human immunodeficiency virus (HIV) have an elevated risk of opioid misuse due to both prescriptions for HIV-associated chronic pain and because injection drug use remains a primary mode of HIV transmission. HIV pathogenesis is characterized by chronic immune activation and microbial dysbiosis, and translocation across the gut barrier exacerbating inflammation. Despite the high rate of co-occurrence, little is known about the microbiome during chronic opioid use in the context of HIV and combination antiretroviral therapy (cART). Read More

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Significant higher-level C-C motif chemokine ligand 2/3 and chemotactic power in cerebral white matter than grey matter in rat and human.

Eur J Neurosci 2021 Mar 16. Epub 2021 Mar 16.

Department of Pharmacology and Experiment Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.

Recent observations indicate that cerebral white matter (WM) exhibits a higher chemoattractant capability for immune cells. The C-C motif chemokine ligands 2 and 3 (CCL2, CCL3) are key chemokines for monocytes and T cells. However, tissue differential of these chemokines is unclear, although the higher CCL2/3 mRNA levels were found in rodent WM. Read More

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Modeling the Effects of Latency Reversing Drugs During HIV-1 and SIV Brain Infection with Implications for the "Shock and Kill" Strategy.

Bull Math Biol 2021 Mar 12;83(4):39. Epub 2021 Mar 12.

Department of Mathematical and Statistical Sciences, University of Alberta, Edmonton, AB, T6G 2G1, Canada.

Combination antiretroviral therapy (cART) has greatly increased life expectancy for human immunodeficiency virus-1 (HIV-1)-infected patients. Even given the remarkable success of cART, the virus persists in many different cells and tissues. The presence of viral reservoirs represents a major obstacle to HIV-1 eradication. Read More

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Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets.

J Neurovirol 2021 Feb 6;27(1):101-115. Epub 2021 Jan 6.

Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.

Despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain prevalent in subjects undergoing therapy. HAND significantly affects individuals' quality of life, as well as adherence to therapy, and, despite the increasing understanding of neuropathogenesis, no definitive diagnostic or prognostic marker has been identified. We investigated transcriptomic profiles in frontal cortex tissues of Simian immunodeficiency virus (SIV)-infected Rhesus macaques sacrificed at different stages of infection. Read More

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February 2021

CRISPR based editing of SIV proviral DNA in ART treated non-human primates.

Nat Commun 2020 11 27;11(1):6065. Epub 2020 Nov 27.

Department of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500N. Broad Street, 7th Floor, Philadelphia, PA, 19140, USA.

Elimination of HIV DNA from infected individuals remains a challenge in medicine. Here, we demonstrate that intravenous inoculation of SIV-infected macaques, a well-accepted non-human primate model of HIV infection, with adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing construct designed for eliminating proviral SIV DNA, leads to broad distribution of editing molecules and precise cleavage and removal of fragments of the integrated proviral DNA from the genome of infected blood cells and tissues known to be viral reservoirs including lymph nodes, spleen, bone marrow, and brain among others. Accordingly, AAV9-CRISPR treatment results in a reduction in the percent of proviral DNA in blood and tissues. Read More

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November 2020

Modeling HIV-1 infection in the brain.

PLoS Comput Biol 2020 11 19;16(11):e1008305. Epub 2020 Nov 19.

Department of Mathematics and Statistics, San Diego State University, San Diego, California, USA.

While highly active antiretroviral therapy (HAART) is successful in controlling the replication of Human Immunodeficiency Virus (HIV-1) in many patients, currently there is no cure for HIV-1, presumably due to the presence of reservoirs of the virus. One of the least studied viral reservoirs is the brain, which the virus enters by crossing the blood-brain barrier (BBB) via macrophages, which are considered as conduits between the blood and the brain. The presence of HIV-1 in the brain often leads to HIV associated neurocognitive disorders (HAND), such as encephalitis and early-onset dementia. Read More

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November 2020

Methamphetamine Increases the Proportion of SIV-Infected Microglia/Macrophages, Alters Metabolic Pathways, and Elevates Cell Death Pathways: A Single-Cell Analysis.

Viruses 2020 11 12;12(11). Epub 2020 Nov 12.

Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Both substance use disorder and HIV infection continue to affect many individuals. Both have untoward effects on the brain, and the two conditions often co-exist. In the brain, macrophages and microglia are infectable by HIV, and these cells are also targets for the effects of drugs of abuse, such as the psychostimulant methamphetamine. Read More

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November 2020

Characterization of Nef expression in different brain regions of SIV-infected macaques.

PLoS One 2020 2;15(11):e0241667. Epub 2020 Nov 2.

Department of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States of America.

Objective: HIV-associated CNS dysfunction is a significant problem among people with HIV (PWH), who now live longer due to viral suppression from combined anti-retroviral therapy (ART). Over the course of infection, HIV generates toxic viral proteins and induces inflammatory cytokines that have toxic effects on neurons in the CNS. Among these viral proteins, HIV Nef has been found in neurons of postmortem brain specimens from PWH. Read More

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December 2020

Opioid-Mediated HIV-1 Immunopathogenesis.

J Neuroimmune Pharmacol 2020 12 8;15(4):628-642. Epub 2020 Oct 8.

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.

Despite the ability of combination antiretroviral therapy to dramatically suppress viremia, the brain continues to be a reservoir of HIV-1 low-level replication. Adding further complexity to this is the comorbidity of drug abuse with HIV-1 associated neurocognitive disorders and neuroHIV. Among several abused drugs, the use of opiates is highly prevalent in HIV-1 infected individuals, both as an abused drug as well as for pain management. Read More

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December 2020

A subtype of cerebrovascular pericytes is associated with blood-brain barrier disruption that develops during normal aging and simian immunodeficiency virus infection.

Neurobiol Aging 2020 12 17;96:128-136. Epub 2020 Aug 17.

Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, USA. Electronic address:

Lax phenotypic characterization of these morphologically distinct pericytes has delayed our understanding of their role in neurological disorders. We herein establish markers which uniquely distinguish different subpopulations of human brain microvascular pericytes and characterize them independently from cerebrovascular smooth muscle cells. Furthermore, we begin to elucidate the roles of these subsets in blood-brain barrier (BBB) breakdown by studying natural aging and simian immunodeficiency virus (SIV) infection in rhesus macaques. Read More

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December 2020

Upregulation of Superoxide Dismutase 2 by Astrocytes in the SIV/Macaque Model of HIV-Associated Neurologic Disease.

J Neuropathol Exp Neurol 2020 09;79(9):986-997

Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

HIV-associated neurocognitive disorders (HAND) remain prevalent despite implementation of antiretroviral therapy (ART). Development of HAND is linked to mitochondrial dysfunction and oxidative stress in the brain; therefore, upregulation of antioxidant defenses is critical to curtail neuronal damage. Superoxide dismutase 2 (SOD2) is a mitochondrial antioxidant enzyme essential for maintaining cellular viability. Read More

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September 2020

Regional Brain Recovery from Acute Synaptic Injury in Simian Immunodeficiency Virus-Infected Rhesus Macaques Associates with Heme Oxygenase Isoform Expression.

J Virol 2020 09 15;94(19). Epub 2020 Sep 15.

Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Brain injury occurs within days in simian immunodeficiency virus (SIV) or human immunodeficiency virus (HIV) infection, and some recovery may occur within weeks. Inflammation and oxidative stress associate with such injury, but what drives recovery is unknown. Chronic HIV infection associates with reduced brain frontal cortex expression of the antioxidant/anti-inflammatory enzyme heme oxygenase-1 (HO-1) and increased neuroinflammation in individuals with cognitive impairment. Read More

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September 2020

A longitudinal study of brain volume changes in rhesus macaque model infected with SIV.

J Neurovirol 2020 08 24;26(4):581-589. Epub 2020 Jun 24.

Department of Radiology, Beijing Youan Hospital, Capital Medical University, No.8, Xi Tou Tiao, Youanmen Wai, Beijing, 10069, Feng Tai District, China.

Given the current lack of understanding of brain volume changes caused by HIV infection, this study aimed to longitudinally assess the changes in regional brain tissue volume following HIV infection and to explore its relationship with peripheral blood absolute CD4+ lymphocyte count (CD4+), the percentage of monocytes in plasma(MON%) and cerebrospinal fluid viral load (CFVL).Four adult male rhesus monkeys were examined in healthy status and following infection with simian immunodeficiency virus using high-resolution 3D T1-weighted sagittal whole brain magnetic resonance imaging. DPABI and SPM were used to process and record changes in brain tissue volume. Read More

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Severer nodular lesion in white matter than in gray matter in simian immunodeficiency virus-infected monkey, but not closely correlated with viral infection.

J Biomed Res 2019 Aug;34(4):292-300

Department of Pharmacology and Experiment Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Immune cell accumulation and white matter anomaly are common features of HIV (human immunodeficiency virus) -infected patients in combination antiretroviral therapy (cART) era. Neuroimaging tests on cART treated patients displayed prominent diffuse white matter lesions. Notably, immune cell nodular lesion (NL) was a conspicuous type of pathological change in HIV/SIV (simian immunodeficiency virus) infected brain before cART. Read More

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HIV-1 Tat-mediated astrocytic amyloidosis involves the HIF-1α/lncRNA BACE1-AS axis.

PLoS Biol 2020 05 26;18(5):e3000660. Epub 2020 May 26.

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.

Increased life expectancy of patients diagnosed with HIV in the current era of antiretroviral therapy is unfortunately accompanied with the prevalence of HIV-associated neurocognitive disorders (HANDs) and risk of comorbidities such as Alzheimer-like pathology. HIV-1 transactivator of transcription (Tat) protein has been shown to induce the production of toxic neuronal amyloid protein and also enhance neurotoxicity. The contribution of astrocytes in Tat-mediated amyloidosis remains an enigma. Read More

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The Brain Retains: Nonhuman Primate Models for Pediatric HIV-1 in the CNS.

Curr HIV/AIDS Rep 2020 08;17(4):343-353

Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.

Purpose Of Review: Perinatal HIV-1 infection is associated with an increased risk for neurologic impairments. With limited access to clinical specimens, animal models could advance our understanding of pediatric central nervous system (CNS) disease and viral persistence. Here, we summarize current findings on HIV-1 CNS infection from nonhuman primate (NHP) models and discuss their implications for improving pediatric clinical outcomes. Read More

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Simian Immunodeficiency Virus-Infected Memory CD4 T Cells Infiltrate to the Site of Infected Macrophages in the Neuroparenchyma of a Chronic Macaque Model of Neurological Complications of AIDS.

mBio 2020 04 21;11(2). Epub 2020 Apr 21.

Laboratory of Molecular Microbiology, NIAID/NIH, Bethesda, Maryland, USA

Simian immunodeficiency virus (SIV)-infected nonhuman primates can serve as a relevant model for AIDS neuropathogenesis. Current SIV-induced encephalitis (SIVE)/neurological complications of AIDS (neuroAIDS) models are generally associated with rapid progression to neuroAIDS, which does not reflect the tempo of neuroAIDS progression in humans. Recently, we isolated a neuropathogenic clone, SIVsm804E-CL757 (CL757), obtained from an SIV-infected rhesus macaque (RM). Read More

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Quantification of Viral RNA and DNA Positive Cells in Tissues From Simian Immunodeficiency Virus/Simian Human Immunodeficiency Virus Infected Controller and Progressor Rhesus Macaques.

Front Microbiol 2019 20;10:2933. Epub 2019 Dec 20.

Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.

Eradication of human immunodeficiency virus 1 (HIV-1) from an infected individual cannot be achieved using current antiretroviral therapy (ART) regimens. Viral reservoirs established in early infection remain unaffected by ART and are able to replenish systemic infection upon treatment interruption. Simian immunodeficiency virus (SIV) infected macaque models are useful for studying HIV pathogenesis, treatments, and persistent viral reservoirs. Read More

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December 2019

Perivascular macrophages in the neonatal macaque brain undergo massive necroptosis after simian immunodeficiency virus infection.

Brain Pathol 2020 05 26;30(3):603-613. Epub 2019 Dec 26.

Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA.

We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV-infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus-induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV-infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid cell populations. Read More

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Brain macrophages harbor latent, infectious simian immunodeficiency virus.

AIDS 2019 12;33 Suppl 2:S181-S188

Department of Molecular and Comparative Pathobiology.

: The current review examines the role of brain macrophages, that is perivascular macrophages and microglia, as a potential viral reservoir in antiretroviral therapy (ART) treated, simian immunodeficiency virus (SIV)-infected macaques. The role, if any, of latent viral reservoirs of HIV and SIV in the central nervous system during ART suppression is an unresolved issue. HIV and SIV infect both CD4 lymphocytes and myeloid cells in blood and tissues during acute and chronic infection. Read More

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December 2019

Nef-induced CCL2 Expression Contributes to HIV/SIV Brain Invasion and Neuronal Dysfunction.

Front Immunol 2019 15;10:2447. Epub 2019 Oct 15.

Institute of Virology, Technische Universität München, Munich, Germany.

C-C motif chemokine ligand 2 (CCL2) is a chemoattractant for leukocytes including monocytes, T cells, and natural killer cells and it plays an important role in maintaining the integrity and function of the brain. However, there is accumulating evidence that many neurological diseases are attributable to a dysregulation of CCL2 expression. Acquired immune deficiency syndrome (AIDS) encephalopathy is a severe and frequent complication in individuals infected with the human immunodeficiency virus (HIV) or the simian immunodeficiency virus (SIV). Read More

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November 2020

Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques.

mBio 2019 08 20;10(4). Epub 2019 Aug 20.

Department of Molecular and Comparative Pathobiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

Human immunodeficiency virus (HIV) eradication or long-term suppression in the absence of antiretroviral therapy (ART) requires an understanding of all viral reservoirs that could contribute to viral rebound after ART interruption. CD4 T cells (CD4s) are recognized as the predominant reservoir in HIV type 1 (HIV-1)-infected individuals. However, macrophages are also infected by HIV-1 and simian immunodeficiency virus (SIV) during acute infection and may persist throughout ART, contributing to the size of the latent reservoir. Read More

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Chronic Binge Alcohol-Associated Differential Brain Region Modulation of Growth Factor Signaling Pathways and Neuroinflammation in Simian Immunodeficiency Virus-Infected Male Macaques.

Alcohol Alcohol 2019 Jan;54(5):477-486

Department of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA.

Aims: Microarray analysis of hippocampal tissue from chronic binge alcohol (CBA)-administered, simian immunodeficiency virus (SIV)-infected male macaques identified altered immune response and neurogenesis as potential mechanisms underlying cognitive deficits in macaques. This study investigated the differential brain region associations between markers of neuroinflammation and growth factor signaling with microtubule-associated protein 2 (MAP2) expression.

Methods: Adult male rhesus macaques were administered CBA (13-14 g EtOH/kg/week, n = 8) or sucrose (SUC, n = 7) beginning 3 months prior to SIV infection and continued until animals reached end-stage disease criteria (3-24 months post infection). Read More

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January 2019

The HIV Reservoir in Monocytes and Macrophages.

Front Immunol 2019 26;10:1435. Epub 2019 Jun 26.

Life Sciences Discipline, Burnet Institute, Melbourne, VIC, Australia.

In people living with HIV (PLWH) who are failing or unable to access combination antiretroviral therapy (cART), monocytes and macrophages are important drivers of pathogenesis and progression to AIDS. The relevance of the monocyte/macrophage reservoir in PLWH receiving cART is debatable as evidence for infected cells is limited and suggests the reservoir is small. Macrophages were assumed to have a moderate life span and lack self-renewing potential, but recent discoveries challenge this dogma and suggest a potentially important role of these cells as long-lived HIV reservoirs. Read More

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October 2020

ICU Interventions in Ischemic Stroke Patients Treated Using Liberalized IV-tPA Criteria.

J Stroke Cerebrovasc Dis 2019 Sep 3;28(9):2488-2495. Epub 2019 Jul 3.

Comprehensive Stroke Care Center, California Pacific Medical Center, California. Electronic address:

Background And Objective: Current standard practice guidelines recommend ICU admission for ischemic stroke patients treated with intravenous tissue plasminogen activator (IV-tPA). More recently, the trend in stroke care is to broaden eligibility for IV thrombolysis. Two examples are a more liberal inclusion criteria known as SMART criteria (sIV-tPA), and the transfer of patients to comprehensive stroke centers (CSC). Read More

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September 2019

SIV-Mediated Synaptic Dysfunction Is Associated with an Increase in Synapsin Site 1 Phosphorylation and Impaired PP2A Activity.

J Neurosci 2019 08 3;39(35):7006-7018. Epub 2019 Jul 3.

Department of Neuroscience, Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania 19140

Although the reduction of viral loads in people with HIV undergoing combination antiretroviral therapy has mitigated AIDS-related symptoms, the prevalence of neurological impairments has remained unchanged. HIV-associated CNS dysfunction includes impairments in memory, attention, memory processing, and retrieval. Here, we show a significant site-specific increase in the phosphorylation of Syn I serine 9, site 1, in the frontal cortex lysates and synaptosome preparations of male rhesus macaques infected with simian immunodeficiency virus (SIV) but not in uninfected or SIV-infected antiretroviral therapy animals. Read More

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Potential Mechanism for HIV-Associated Depression: Upregulation of Serotonin Transporters in SIV-Infected Macaques Detected by 11C-DASB PET.

Front Psychiatry 2019 23;10:362. Epub 2019 May 23.

Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences,Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States.

Increased incidence of depression in HIV+ patients is associated with lower adherence to treatment and increased morbidity/mortality. One possible underlying pathophysiology is serotonergic dysfunction. In this study, we used an animal model of HIV, the SIV-infected macaque, to longitudinally image serotonin transporter (SERT) expression before and after inoculation, using 11C-DASB (SERT ligand) PET imaging. Read More

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