Susceptibility of Primary Human Glial Fibrillary Acidic Protein-Positive Brain Cells to Human Immunodeficiency Virus Infection In Vitro: Anti-HIV Activity of Memantine

Rytik, Peter G.; Vf, Eremin; Kvacheva, Z. B.; Poleschuk, Nikolai N.; Popov, S.; Schröder, Heinz C.; Bachmann, Michael; Weiler, Barbara E.; Müller, Wernér E.G.

doi:10.1089/aid.1991.7.89

Cited by 26 publications

(13 citation statements)

References 42 publications

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“…HIV infects several cell types in the brain and nervous system, and multiple studies also suggest compartmentalized CNS virus[72-79]. In vitro infection of astrocytes[80,81] and fetal neural cells[82] and productive infection of fetal glial cells[83], human brain microglia[84], and human brain capillary endothelial cells[85] have each been demonstrated. Both nonproductive[86], and (transiently) productive infection of astrocytes and astroglial cells have been described including transient productive infection followed by viral latency that is reversible[81].…”

Section: Nervous Systemmentioning

confidence: 99%

Tissue reservoirs of HIV

Wong

Yukl

2016

Current Opinion in HIV and AIDS

195

161

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Purpose Tissue reservoirs of HIV may promote the persistent immunopathology responsible for non-AIDS morbidity and data support multifocal reactivation from tissues as the source of viral rebound during ART interruption. The heterogeneity of tissue reservoirs and incomplete knowledge about their composition are obstacles to an HIV cure. Recent findings In addition to the higher concentration of infected CD4+ T cells found in both central lymphoid tissues and gut, specific subsets of CD4+ T cells appear to play a disproportionate role in HIV persistence. Recently, a subset of central memory T cells enriched in lymphnode germinal centers called T-follicular helper cells have been identified that express more viral RNA and occupy an anatomic niche inaccessible to CTL killing. Additional observations suggest that ARV concentrations may be lower in some tissues raising the possibility for localized, low-level viral replication. Finally, some recent data implicate the persistence of infected, non-CD4+ T cell types in tissues during ART. Summary The retention of infected cells in a wide variety of tissues, often with distinct viral and cellular characteristics, underscores the importance of studying tissue reservoirs in the development and assessment of cure strategies. Both inhibitory ARVs and latency reversing drugs must reach these sites and novel strategies may be needed to attack virus in cells as variable as Tfh and macrophages.

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Section: Nervous Systemmentioning

confidence: 99%

Tissue reservoirs of HIV

Wong

Yukl

2016

Current Opinion in HIV and AIDS

195

161

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“…Moreover, the neuroprotective properties of memantine have been described in other contexts, such as cerebral ischemia (29). In AIDS, memantine appears to inhibit neuronal damage promoted by the viral protein gp120 (30–33). …”

Section: Introductionmentioning

confidence: 99%

N -Methyl- d -Aspartate (NMDA) Receptor Blockade Prevents Neuronal Death Induced by Zika Virus Infection

Costa

Sarto

Rocha

et al. 2017

mBio

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Zika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by N-methyl-d-aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells. Moreover, in vivo experiments demonstrate that therapeutic memantine treatment prevents the increase of intraocular pressure (IOP) induced by infection and massively reduces neurodegeneration and microgliosis in the brain of infected mice. Our results indicate that the blockade of NMDARs by memantine provides potent neuroprotective effects against ZIKV-induced neuronal damage, suggesting it could be a viable treatment for patients at risk for ZIKV infection-induced neurodegeneration.

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“…For example, statins have broad spectrum antimicrobial effects (certain oral bacteria as well as viruses and fungi) [243], while NSAIDs have antibacterial effects related to an ability to inhibit bacterial DNA replication [244]. Melatonin also has antimicrobial effects against bacteria and viruses [245] and memantine also has antiviral effects against a neurotropic strain (HCoV-OC43) of a human respiratory coronavirus [246] as well as the influenza or HIV-1 viruses [247,248].…”

Section: Other Environmental Risk Factors In Ad Disrupt the Bbb And Bmentioning

confidence: 99%

Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer’s Disease

Carter

2017

ADR

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Diverse pathogens are detected in Alzheimer’s disease (AD) brains. A bioinformatics survey showed that AD genome-wide association study (GWAS) genes (localized in bone marrow, immune locations and microglia) relate to multiple host/pathogen interactomes (Candida albicans, Cryptococcus neoformans, Bornavirus, Borrelia burgdorferri, cytomegalovirus, Ebola virus, HSV-1, HERV-W, HIV-1, Epstein-Barr, hepatitis C, influenza, Chlamydia pneumoniae, Porphyrymonas gingivalis, Helicobacter pylori, Toxoplasma gondii, Trypanosoma cruzi). These interactomes also relate to the AD hippocampal transcriptome and to plaque or tangle proteins. Upregulated AD hippocampal genes match those upregulated by multiple bacteria, viruses, fungi, or protozoa in immunocompetent cells. AD genes are enriched in GWAS datasets reflecting pathogen diversity, suggesting selection for pathogen resistance, as supported by the old age of AD patients, implying resistance to earlier infections. APOE4 is concentrated in regions of high parasitic burden and protects against childhood tropical infections and hepatitis C. Immune/inflammatory gain of function applies to APOE4, CR1, and TREM2 variants. AD genes are also expressed in the blood-brain barrier (BBB), which is disrupted by AD risk factors (age, alcohol, aluminum, concussion, cerebral hypoperfusion, diabetes, homocysteine, hypercholesterolemia, hypertension, obesity, pesticides, pollution, physical inactivity, sleep disruption, smoking) and by pathogens, directly or via olfactory routes to basal-forebrain BBB control centers. The BBB benefits from statins, NSAIDs, estrogen, melatonin, memantine, and the Mediterranean diet. Polymicrobial involvement is supported by upregulation of bacterial, viral, and fungal sensors/defenders in the AD brain, blood, or cerebrospinal fluid. AD serum amyloid-β autoantibodies may attenuate its antimicrobial effects favoring microbial survival and cerebral invasion leading to activation of neurodestructive immune/inflammatory processes, which may also be augmented by age-related immunosenescence. AD may thus respond to antibiotic, antifungal, or antiviral therapy.

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Susceptibility of Primary Human Glial Fibrillary Acidic Protein-Positive Brain Cells to Human Immunodeficiency Virus Infection In Vitro: Anti-HIV Activity of Memantine

Cited by 26 publications

References 42 publications

Tissue reservoirs of HIV

Tissue reservoirs of HIV

N -Methyl- d -Aspartate (NMDA) Receptor Blockade Prevents Neuronal Death Induced by Zika Virus Infection

Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer’s Disease

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