Neuronal activity regulates viral replication of herpes simplex virus type 1 in the nervous system

Zhang, Cheryl X; Ofiyai, Harrison; He, Min; Bu, Xuexian; Wen, Yanhua; Jia, William

doi:10.1080/13550280590952781

Cited by 19 publications

(21 citation statements)

References 59 publications

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“…Most notably, amino acid metabolic profiling detected significant changes in three non-aromatic amino acids that function as CNS neurotransmitters (aspartate, glutamate, and glycine) and two aromatic amino acids (phenylalanine and tyrosine) that are upstream precursors to two other CNS neurotransmitters, dihydroxyphenylalanine and dopamine [36]. Without regard to the etiopathology of any neurological disease state, this altered amino acid profile is noteworthy in light of previous studies linking other neurotropic viral infections with CNS neurotransmitter dysregulation [37].…”

Section: Discussionmentioning

confidence: 77%

Borna Disease Virus Infection Perturbs Energy Metabolites and Amino Acids in Cultured Human Oligodendroglia Cells

et al. 2012

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BackgroundBorna disease virus is a neurotropic, non-cytolytic virus that has been widely employed in neuroscientific research. Previous studies have revealed that metabolic perturbations are associated with Borna disease viral infection. However, the pathophysiological mechanism underlying its mode of action remains unclear.MethodologyHuman oligodendroglia cells infected with the human strain Borna disease virus Hu-H1 and non-infected matched control cells were cultured in vitro. At day 14 post-infection, a proton nuclear magnetic resonance-based metabonomic approach was used to differentiate the metabonomic profiles of 28 independent intracellular samples from Borna disease virus-infected cells (n = 14) and matched control cells (n = 14). Partial least squares discriminant analysis was performed to demonstrate that the whole metabonomic patterns enabled discrimination between the two groups, and further statistical testing was applied to determine which individual metabolites displayed significant differences between the two groups.FindingsMetabonomic profiling revealed perturbations in 23 metabolites, 19 of which were deemed individually significant: nine energy metabolites (α-glucose, acetate, choline, creatine, formate, myo-inositol, nicotinamide adenine dinucleotide, pyruvate, succinate) and ten amino acids (aspartate, glutamate, glutamine, glycine, histidine, isoleucine, phenylalanine, threonine, tyrosine, valine). Partial least squares discriminant analysis demonstrated that the whole metabolic patterns enabled statistical discrimination between the two groups.ConclusionBorna disease viral infection perturbs the metabonomic profiles of several metabolites in human oligodendroglia cells cultured in vitro. The findings suggest that Borna disease virus manipulates the host cell’s metabolic network to support viral replication and proliferation.

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Section: Discussionmentioning

confidence: 77%

Borna Disease Virus Infection Perturbs Energy Metabolites and Amino Acids in Cultured Human Oligodendroglia Cells

et al. 2012

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“…Because KCl treatment causes excitotoxicity in neurons and has been previously reported to reduce HSV-1 replication [30], we next pursued an optogenetics approach to modulate neuronal firing activity. Channelrhodopsin 2 (ChR2) is a light-gated ion channel originally isolated from algae, which has become a popular tool to control the activity of neurons using light [31].…”

Section: Resultsmentioning

confidence: 99%

Alpha Herpesvirus Egress and Spread from Neurons Uses Constitutive Secretory Mechanisms Independent of Neuronal Firing Activity

Ambrosini

Deshmukh

Berry

et al. 2019

Preprint

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Alpha herpesviruses naturally infect the peripheral nervous system, and can spread to the central nervous system causing severe deadly or debilitating disease. Because alpha herpesviruses spread along synaptic circuits, and infected neurons exhibit altered electrophysiology and increased spontaneous firing, we hypothesized that alpha herpesviruses use activity-dependent synaptic vesicle-like regulated secretory mechanisms for egress and spread from neurons. To address this hypothesis, we used a compartmentalized primary neuron culture system to measure egress and spread of pseudorabies virus (PRV), pharmacological and optogenetics approaches to modulate neuronal firing activity, and a live-cell fluorescence microscopy assay to directly visualize the exocytosis of individual virus particles from infected neurons. Using tetrodotoxin to silence neuronal activity, we observed no inhibition of virus spread, and using potassium chloride or optogenetics to elevate neuronal activity, we also show no increase in virus spread. Using a live-cell fluorescence microscopy method to directly measure virus egress from infected neurons, we observed no association between virus particle exocytosis and intracellular Ca2+ signaling. Finally, we observed virus particle exocytosis occurs in association with constitutive secretory Rab GTPases, Rab6a and Rab8a, not Rab proteins that are associated with the Ca2+-regulated secretory pathway in neurons, Rab3a and Rab11a. Therefore, we conclude that alpha herpesvirus egress and spread is independent of neuronal activity and Ca2+ signaling because virus particle exocytosis uses constitutive secretory mechanisms in neurons.Author SummaryAlpha herpesviruses, including important human pathogens Herpes Simplex Virus 1 and 2, and Varicella-Zoster Virus, are among the very few viruses that naturally infect the nervous system. These viruses cause recurrent herpetic and zosteriform lesions, peripheral neuropathies, and deadly or debilitating central nervous system diseases. Many of the molecular and cellular mechanisms of viral egress and spread remain unknown, particularly in the context of specialized neuronal cell biology. Our results indicate that elevated firing activity of infected neurons is not functionally or mechanistically linked to virus egress and spread; therefore, therapies targeting peripheral neuropathic symptoms, elevated neuronal activity, and synaptic vesicle secretory mechanisms are unlikely to affect virus spread in the nervous system.

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“…Our study was designed to evaluate whether the expression of chosen subunits of GABA A receptors in PBMCs bears any relation to HCV infection and/or the path of HCV RNA elimination after anti-viral treatment. Studies that were carried out on other viruses like herpes simplex virus (HSV) and human immunodeficiency virus (HIV) indicated that the expression of GABA A receptor on the target cells could be modulated upon the viral infection [18, 19]. Although GABA A receptors tend to exist as a pentameric structure consisting of six major GABA A receptor subunits [1], we decided to screen the expression of two of them: α1 and β3.…”

Section: Discussionmentioning

confidence: 99%

The altered expression of α1 and β3 subunits of the gamma-aminobutyric acid A receptor is related to the hepatitis C virus infection

Sidorkiewicz

Brocka

Bronis

et al. 2011

Eur J Clin Microbiol Infect Dis

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The modulation of the gamma-aminobutyric acid type A (GABA A) receptors activity was observed in several chronic hepatitis failures, including hepatitis C. The expression of GABA A receptor subunits α1 and β3 was detected in peripheral blood mononuclear cells (PBMCs) originated from healthy donors. The aim of the study was to evaluate if GABA A α1 and β3 expression can also be observed in PBMCs from chronic hepatitis C (CHC) patients and to evaluate a possible association between their expression and the course of hepatitis C virus (HCV) infection. GABA A α1- and β3-specific mRNAs presence and a protein expression in PBMCs from healthy donors and CHC patients were screened by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. In patients, HCV RNA was determined in sera and PBMCs. It was shown that GABA A α1 and β3 expression was significantly different in PBMCs from CHC patients and healthy donors. In comparison to healthy donors, CHC patients were found to present an increase in the expression of GABA A α1 subunit and a decrease in the expression of β3 subunit in their PBMCs. The modulation of α1 and β3 GABA A receptors subunits expression in PBMCs may be associated with ongoing or past HCV infection.

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Neuronal activity regulates viral replication of herpes simplex virus type 1 in the nervous system

Cited by 19 publications

References 59 publications

Borna Disease Virus Infection Perturbs Energy Metabolites and Amino Acids in Cultured Human Oligodendroglia Cells

Borna Disease Virus Infection Perturbs Energy Metabolites and Amino Acids in Cultured Human Oligodendroglia Cells

Alpha Herpesvirus Egress and Spread from Neurons Uses Constitutive Secretory Mechanisms Independent of Neuronal Firing Activity

The altered expression of α1 and β3 subunits of the gamma-aminobutyric acid A receptor is related to the hepatitis C virus infection

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