Type I Interferons in NeuroHIV

Infection with Human Immunodeficiency Virus (HIV)-1 continues to cause HIV-associated neurocognitive disorders despite combined antiretroviral therapy. Interferons (IFNs) are important for any antiviral immune response, but the lasting production of IFNα causes exhaustive activation leading eventually to progression to AIDS. Expression of IFNα in the HIV-exposed central nervous system has been linked to cognitive impairment and inflammatory neuropathology. In contrast, IFNβ exerts anti-inflammatory effects, appears to control, at least temporarily, lentiviral infection in the brain and provides neuroprotection. The dichotomy of type I IFN effects on HIV-1 infection and the associated brain injury will be discussed in this review, because the underlying mechanisms require further investigation to allow harnessing these innate immune factors for therapeutic purposes.

• Publication year

  2019

• Venue

  Viral immunology

• Publication date

  2019-01-09

• Fields of study

  Medicine

• Identifiers
  DOI 10.1089/vim.2018.0085PMID 30260742PMCID PMC6350057
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• HIV-1 Infection and Type 1 Interferon: Navigating Through Uncertain Waters

  2019cited by this paper
• Interferon-associated therapies toward HIV control: The back and forth.

  2018cited by this paper
• Pegylated Interferon-&agr;–Induced Natural Killer Cell Activation Is Associated With Human Immunodeficiency Virus-1 DNA Decline in Antiretroviral Therapy–Treated HIV-1/Hepatitis C Virus–Coinfected Patients

  2018cited by this paper
• Interferon-α Subtypes As an Adjunct Therapeutic Approach for Human Immunodeficiency Virus Functional Cure

  2018cited by this paper
• Impairment of the type I interferon response by HIV-1: Potential targets for HIV eradication.

  2017cited by this paper
• IFNβ Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain Injury

  2017cited by this paper
• Targeting type I interferon–mediated activation restores immune function in chronic HIV infection

  2017cited by this paper
• Update and New Directions in Therapeutics for Neurological Complications of HIV Infections

  2016cited by this paper
• HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment

  2016cited by this paper
• Interferons and HIV Infection: The Good, the Bad, and the Ugly

  2016cited by this paper
• Current views on interferon therapy for HIV

  2016cited by this paper
• Cerebrospinal fluid interferon alpha levels correlate with neurocognitive impairment in ambulatory HIV-Infected individuals

  2016cited by this paper
• Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson’s Disease-like Dementia

  2015cited by this paper
• Type I IFN--a blunt spear in fighting HIV-1 infection.

  2015influential reference
• The molecular basis for functional plasticity in type I interferon signaling.

  2015cited by this paper
• CNS-specific regulatory elements in brain-derived HIV-1 strains affect responses to latency-reversing agents with implications for cure strategies

  2015cited by this paper
• HIV-1 and interferons: who's interfering with whom?

  2015influential reference
• Pillars Article: Virus Interference. I. The Interferon. Proc R Soc Lond B Biol Sci. 1957. 147: 258-267.

  2015cited by this paper
• CCR5 Knockout Prevents Neuronal Injury and Behavioral Impairment Induced in a Transgenic Mouse Model by a CXCR4-Using HIV-1 Glycoprotein 120

  2014cited by this paper
• Eradication of human immunodeficiency virus from brain reservoirs

  2014cited by this paper
• Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression

  2014influential reference
• Regulation of type I interferon responses

  2013influential reference
• A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus

  2013cited by this paper
• Enhanced Human Immunodeficiency Virus Type 1 Expression and Neuropathogenesis in Knockout Mice Lacking Type I Interferon Responses

  2013cited by this paper
• HIV Restriction Factors and Mechanisms of Evasion.

  2012cited by this paper
• The National NeuroAIDS Tissue Consortium Brain Gene Array: Two Types of HIV-Associated Neurocognitive Impairment

  2012cited by this paper
• Canonical Type I IFN Signaling in Simian Immunodeficiency Virus-Infected Macrophages Is Disrupted by Astrocyte-Secreted CCL2

  2012cited by this paper
• Commensal bacteria calibrate the activation threshold of innate antiviral immunity.

  2012cited by this paper
• Mitogen-Activated Protein Kinase p38 in HIV Infection and Associated Brain Injury

  2011cited by this paper
• A diverse array of gene products are effectors of the type I interferon antiviral response

  2011cited by this paper
• Simian Immunodeficiency Virus Infection in the Brain and Lung Leads to Differential Type I IFN Signaling during Acute Infection

  2011cited by this paper
• Innate immune responses and control of acute simian immunodeficiency virus replication in the central nervous system

  2011influential reference
• Innate Sensing of HIV-Infected Cells

  2011cited by this paper
• Downregulation of Robust Acute Type I Interferon Responses Distinguishes Nonpathogenic Simian Immunodeficiency Virus (SIV) Infection of Natural Hosts from Pathogenic SIV Infection of Rhesus Macaques

  2010cited by this paper
• HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy

  2010cited by this paper
• Activation of p38 MAPK Is Required in Monocytic and Neuronal Cells for HIV Glycoprotein 120-Induced Neurotoxicity

  2010cited by this paper
• Rebuilding synaptic architecture in HIV-1 associated neurocognitive disease: A therapeutic strategy based on modulation of mixed lineage kinase

  2010cited by this paper
• Suppressor of Cytokine Signaling 3 Inhibits Antiviral IFN-β Signaling To Enhance HIV-1 Replication in Macrophages

  2010cited by this paper
• HIV-Associated Neurocognitive Disorder: Pathogenesis and Therapeutic Opportunities

  2010cited by this paper
• Intracellular toll-like receptors.

  2010cited by this paper
• Characterization of the Alpha Interferon-Induced Postentry Block to HIV-1 Infection in Primary Human Macrophages and T Cells

  2010cited by this paper
• Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys.

  2009cited by this paper
• Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response.

  2009cited by this paper
• The immune response during acute HIV-1 infection: clues for vaccine development

  2009cited by this paper
• Interferon-α Causes Neuronal Dysfunction in Encephalitis

  2009cited by this paper
• Astrocytes produce interferon‐alpha and CXCL10, but not IL‐6 or CXCL8, in aicardi‐Goutières syndrome

  2008cited by this paper
• HIV and antiretroviral therapy in the brain: neuronal injury and repair

  2008cited by this paper
• Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections

  2008cited by this paper
• HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection

  2007cited by this paper
• Interferon-beta

  2007cited by this paper
• Type I interferon response in the central nervous system.

  2007cited by this paper
• Copolymer-1 Induces Adaptive Immune Anti-inflammatory Glial and Neuroprotective Responses in a Murine Model of HIV-1 Encephalitis1

  2007cited by this paper
• Cognitive dysfunction in HIV encephalitic SCID mice correlates with levels of Interferon-α in the brain

  2007cited by this paper
• HIV/gp120 decreases adult neural progenitor cell proliferation via checkpoint kinase-mediated cell-cycle withdrawal and G1 arrest.

  2007cited by this paper
• Interferon, a growing cytokine family: 50 years of interferon research.

  2007cited by this paper
• Inhibition of Mixed Lineage Kinase 3 Prevents HIV-1 Tat-Mediated Neurotoxicity and Monocyte Activation1

  2006cited by this paper
• Neural progenitors and HIV-1-associated central nervous system disease in adults and children.

  2006cited by this paper
• Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors.

  2006cited by this paper
• Mechanism for the establishment of transcriptional HIV latency in the brain in a simian immunodeficiency virus-macaque model.

  2006cited by this paper
• Interferon signalling network in innate defence

  2006cited by this paper
• Type I Inteferon Gene Induction by the Interferon Regulatory Factor Family of Transcription Factors

  2006cited by this paper
• HIV-infection of the central nervous system: the tightrope walk of innate immunity.

  2005cited by this paper
• Differential involvement of p38 and JNK MAP kinases in HIV-1 Tat and gp120-induced apoptosis and neurite degeneration in striatal neurons.

  2005cited by this paper
• Interferon beta promotes nerve growth factor secretion early in the course of multiple sclerosis.

  2005cited by this paper
• Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions.

  2005cited by this paper
• HIV-1 infection and AIDS: consequences for the central nervous system

  2005cited by this paper
• Interferon and the central nervous system.

  2005cited by this paper
• A mouse model for study of systemic HIV-1 infection, antiviral immune responses, and neuroinvasiveness.

  2005cited by this paper
• Patterns of gene dysregulation in the frontal cortex of patients with HIV encephalitis.

  2004cited by this paper
• HIV-1 promotes quiescence in human neural progenitor cells.

  2004cited by this paper
• An update on the neuropathology of HIV in the HAART era

  2004cited by this paper
• Multinucleated giant cells in brain: A hallmark of the acquired immune deficiency syndrome (AIDS)

  2004cited by this paper
• Cree encephalitis is allelic with Aicardi-Goutiéres syndrome: implications for the pathogenesis of disorders of interferon alpha metabolism

  2003cited by this paper
• Immune responses to RNA-virus infections of the CNS

  2003cited by this paper
• IFN-β Gene Deletion Leads to Augmented and Chronic Demyelinating Experimental Autoimmune Encephalomyelitis1

  2003cited by this paper
• Human immunodeficiency virus-associated dementia: An evolving disease

  2003cited by this paper
• The interferon in TLR signaling: more than just antiviral.

  2003cited by this paper
• Interferon‐β activates multiple signaling cascades in primary human microglia

  2002cited by this paper
• Interferon-beta activates multiple signaling cascades in primary human microglia.

  2002cited by this paper
• Transforming growth factor beta-1 and interferon-alpha in the AIDS dementia complex (ADC): possible relationship with cerebral viral load?

  2001cited by this paper
• Pathways to neuronal injury and apoptosis in HIV-associated dementia

  2001cited by this paper
• CXCR4-activated astrocyte glutamate release via TNFα: amplification by microglia triggers neurotoxicity

  2001cited by this paper
• Transforming growth factor beta-1 and interferon-alpha in the aids dementia complex: possible relationship with cerebral viral load?

  2001cited by this paper
• Control of Sindbis Virus Infection by Antibody in Interferon-Deficient Mice

  2000cited by this paper
• CXCR4 mediates entry and productive infection of syncytia-inducing (X4) HIV-1 strains in primary macrophages.

  2000cited by this paper
• Differential induction of chemokines in human microglia by type i and ii interferons

  2000cited by this paper
• Distinct patterns of stimulus‐inducible chemokine mRNA accumulation in human fetal astrocytes and microglia

  2000cited by this paper
• Uptake of HIV-1 Tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands

  2000cited by this paper
• Role of MIP-1beta and RANTES in HIV-1 infection of microglia: inhibition of infection and induction by IFNbeta.

  2000cited by this paper
• HIV Infection and Dementia

  2000cited by this paper
• Alpha/Beta Interferon Protects Adult Mice from Fatal Sindbis Virus Infection and Is an Important Determinant of Cell and Tissue Tropism

  2000cited by this paper
• Age‐related behavioural deficits in transgenic mice expressing the HIV‐1 coat protein gp120

  1999cited by this paper
• HIV‐1 Tat‐Mediated Activation of Glycogen Synthase Kinase‐3β Contributes to Tat‐Mediated Neurotoxicity

  1999cited by this paper
• Measuring HIV-1 RNA and interferon-alpha in the cerebrospinal fluid of AIDS patients: insights into the pathogenesis of AIDS Dementia Complex.

  1999cited by this paper
• Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis.

  1999cited by this paper
• HIV-1 protein Tat induces apoptosis of hippocampal neurons by a mechanism involving caspase activation, calcium overload, and oxidative stress.

  1998cited by this paper
• Selective inhibition of human glial inducible nitric oxide synthase by interferon‐β: Implications for multiple sclerosis

  1998cited by this paper
• Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1 alpha is mediated by the chemokine receptor CXCR4.

  1998cited by this paper
• Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity.

  1998cited by this paper
• Is interferon-alpha a neuromodulator?

  1998cited by this paper

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  2026cites this paper
• IFN response regulation upon viral infections.

  2026cites this paper
• Persistent type I interferon signaling within the brain of people with HIV on ART with cognitive impairment

  2025cites this paper
• Assessment of CD4+ T cell recovery after direct-acting antiviral hepatitis C treatment in HIV/HCV coinfected immunological nonresponders to ART

  2025cites this paper
• A novel glia-immune humanized mouse model for investigating neuroimmune mechanisms in CNS HIV infection and diverse neurological disorders

  2025cites this paper
• Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection

  2024cites this paper
• Interferon-β deficiency alters brain response to chronic HIV-1 envelope protein exposure in a transgenic model of NeuroHIV.

  2024cites this paper
• Cannabinoids modulate the microbiota–gut–brain axis in HIV/SIV infection by reducing neuroinflammation and dysbiosis while concurrently elevating endocannabinoid and indole-3-propionate levels

  2023cites this paper
• Occludin regulates HIV-1 infection by modulation of the interferon stimulated OAS gene family

  2023cites this paper
• Viruses - a major cause of amyloid deposition in the brain

  2023influential citation
• Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management

  2023cites this paper
• Trained immunity in viral infections, Alzheimer's disease and multiple sclerosis: A convergence in type I interferon signalling and IFNβ-1a.

  2022cites this paper
• Sympathetic Nerves and Innate Immune System in the Spleen: Implications of Impairment in HIV-1 and Relevant Models

  2022cites this paper
• Innate Immune Sensing of Viruses and Its Consequences for the Central Nervous System

  2021cites this paper
• Red Algal Sulfated Galactan Binds and Protects Neural Cells from HIV-1 gp120 and Tat

  2021cites this paper
• Outside-in induction of the IFITM3 trafficking system by infections, including SARS-CoV-2, in the pathobiology of Alzheimer’s disease

  2021cites this paper
• Neuroinflammation associates with antioxidant heme oxygenase-1 response throughout the brain in persons living with HIV

  2020cites this paper
• A pivotal role for Interferon-α receptor-1 in neuronal injury induced by HIV-1

  2020cites this paper
• Pregnane steroidogenesis is altered by HIV-1 Tat and morphine: Physiological allopregnanolone is protective against neurotoxic and psychomotor effects

  2020cites this paper
• Differential Contribution of HIV-1 Subtypes B and C to Neurological Disorders: Mechanisms and Possible Treatments.

  2019cites this paper
• Type I interferons in host defence and inflammatory diseases

  2019cites this paper
• Neuroinflammation & pre-mature aging in the context of chronic HIV infection and drug abuse: Role of dysregulated autophagy.

  2019cites this paper
• A Novel Glia-immune humanized mouse model for investigation of HIV CNS infection and 1 neuroinflammation. 2

  year unknowncites this paper