Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Glutamine supplementation suppresses herpes simplex virus reactivation III

ABSTRACT: Chronic viral infections are difficult to treat and new approaches, particularly those involving enhancing immune responses are needed. Herpes simplex virus (HSV) establishes latency, reactivates frequently, and breakthrough reactivation can occur despite suppressive antiviral therapy. Virus-specific T cells are important to control HSV, and activated T cells require increased metabolism of glutamine for their proliferation. We found that treatment of HSV-1 latently infected mice and HSV-2 infected guinea pigs with supplemental oral glutamine reduced virus reactivation. Transcriptome analysis of mice treated with glutamine showed that several interferon (IFN)-γ inducible genes were upregulated. Unlike wild-type mice, supplemental glutamine was ineffective in reducing the rate of HSV-1 reactivation in IFN-γ knock-out mice. Mice treated with glutamine had higher numbers of HSV-specific IFN-γ producing CD8 T cells in latently infected ganglia. Thus, glutamine may enhance the IFN-γ-associated immune response and reduce the rate of reactivation of latent virus infection.

ORGANISM(S): Mus musculus

PROVIDER: GSE95715 | GEO | 2017/08/30

SECONDARY ACCESSION(S): PRJNA378217

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Glutamine supplementation suppresses herpes simplex virus reactivation II

Project description:Chronic viral infections are difficult to treat and new approaches, particularly those involving enhancing immune responses are needed. Herpes simplex virus (HSV) establishes latency, reactivates frequently, and breakthrough reactivation can occur despite suppressive antiviral therapy. Virus-specific T cells are important to control HSV, and activated T cells require increased metabolism of glutamine for their proliferation. We found that treatment of HSV-1 latently infected mice and HSV-2 infected guinea pigs with supplemental oral glutamine reduced virus reactivation. Transcriptome analysis of mice treated with glutamine showed that several interferon (IFN)-γ inducible genes were upregulated. Unlike wild-type mice, supplemental glutamine was ineffective in reducing the rate of HSV-1 reactivation in IFN-γ knock-out mice. Mice treated with glutamine had higher numbers of HSV-specific IFN-γ producing CD8 T cells in latently infected ganglia. Thus, glutamine may enhance the IFN-γ-associated immune response and reduce the rate of reactivation of latent virus infection.

2017-08-30 | GSE95714 | GEO

Glutamine supplementation suppresses herpes simplex virus reactivation I

2017-08-30 | GSE95713 | GEO

Immune Escape via A Transient Gene Expression Program Enables Productive Replication of A Latent Pathogen

Project description:How type I / II interferons (IFNs) prevent periodic re-emergence of latent pathogens in tissues of diverse cell-types remains unknown. Using homogenous neuron cultures latently-infected with herpes simplex virus (HSV), we show that extrinsic type I or II IFN act directly on neurons to induce unique gene expression signatures and inhibit the reactivation-specific burst of viral genome-wide transcription called Phase I. Surprisingly, IFNs suppressed reactivation only during a limited period early in Phase I preceding productive virus growth. Sensitivity to type II IFN was selectively lost if viral ICP0, which normally accumulates later in Phase I, was expressed prior to reactivation. Thus, IFNs suppress reactivation by preventing initial expression of latent genomes but are ineffective once Phase I viral proteins accumulate and limit IFN action. This demonstrates that inducible reactivation from latency is only transiently sensitive to IFNs. Moreover, it illustrates how latent pathogens escape host immune control to periodically replicate by rapidly deploying an interferon-resistant state.

2017-02-03 | GSE90744 | GEO

Kidney gene expression profile following the transplant-induced reactivation of MCMV

Project description:Reactivation of latent HCMV is a significant infectious complication of organ transplantation, and current therapies target viral replication once reactivation of transcriptionally silent, latent virus has already occurred. The specific molecular pathways that activate viral gene expression are not well understood. Our studies aim to identify these factors, with the goal of developing novel therapies that prevent transcriptional reactivation in transplant recipients. MCMV is a valuable model for studying latency and reactivation of CMV induced by organ transplantation. We previously demonstrated that transplantation of MCMV-latently infected kidneys into allogeneic recipients induces transcriptional reactivation of immediate early (IE) gene expression within 48 hr. We used microarrays to profile global mouse kidney gene expression associated with transcriptional reactivation of MCMV immediate early gene expression at 48 hr after transplant of MCMV latently infected kidneys into allogeneic recipients. We identified differentially expressed genes and pathways associated with both early acute rejection and reactivation of MCMV. control vs. allograft

2015-08-27 | E-GEOD-72392 | biostudies-arrayexpress

Therapeutic Prime/Pull Vaccination of HSV-2 Infected Guinea Pigs with the Ribonucleotide Reductase 2 (RR2) and CXCL11 boosts TRM and TEM CD4+/CD8+ T cells to protect from recurrent genital herpes

Project description:Following acute herpes simplex virus type 2 (HSV-2) infection, the virus undergoes an asymptomatic latent infection of sensory neurons of dorsal root ganglia (DRG). Chemical and physical stress cause intermittent virus reactivation from latently infected DRG and recurrent virus shedding in the genital mucosal epithelium causing genital herpes in symptomatic patients. While T-cells appear to play a role in controlling virus reactivation from DRG and reducing the severity of recurrent genital herpes, the mechanisms for recruiting these T-cells into DRG and the vaginal mucosa (VM) remain to be fully elucidated. The present study investigates the effect of CXCL9, CXCL10, and CXCL11 T-cell-attracting chemokines on the frequency and function of DRG- and VM-resident CD4+ and CD8+ T cells and its effect on the frequency and severity of recurrent genital herpes in the recurrent herpes guinea pig model. HSV-2 latent-infected guinea pigs were immunized intramuscularly with the HSV-2 RR2 protein (Prime) and subsequently treated intravaginally with the neurotropic adeno-associated virus type 8 (AAV-8) expressing CXCL9, CXCL10, or CXCL11 chemokines to recruit CD4+ and CD8+ T cells into the infected DRG and VM (Pull). Compared to the RR2 therapeutic vaccine alone, the RR2/CXCL11 prime/pull therapeutic vaccine significantly increased the frequencies of functional tissue-resident (TRM cells) and effector (TEM cells) memory CD4+ and CD8+ T cells in both DRG and VM tissues. This was associated with less virus in the healed genital mucosal epithelium and reduced frequency and severity of recurrent genital herpes. These findings confirm the role of local DRG- and VM-resident CD4+ and CD8+ T cells in reducing virus shedding at the vaginal site of infection and the severity of recurrent genital herpes and propose the novel prime-pull vaccine strategy to protect against recurrent genital herpes.

2024-03-14 | GSE261599 | GEO

IFN-λ signaling protects mice from severe HSV-1 skin disease II

Project description:Type III interferons (IFN-λ) are antiviral and immunomodulatory cytokines that have been best characterized in respiratory and gastrointestinal infections, but the effects of IFN-λ against skin infections have not been extensively investigated. We sought to define the skin-specific effects of IFN-λ against the highly prevalent human pathogen herpes simplex virus (HSV). We infected mice lacking the IFN-λ receptor (Ifnlr1-/-), both the IFN-λ and the IFN-αβ receptor (Ifnar1-/- Ifnlr1-/-), or IFN-λ cytokines (Ifnl2/3-/-) and found that IFN-λ restricts the severity of HSV-1 and HSV-2 skin lesions, independent of a direct effect on viral load. Using conditional knockout mice, we found that IFN-λ signaling in both keratinocytes and neutrophils was necessary to control HSV-1 skin lesion severity, and that IFN-λ signaling in keratinocytes suppressed CXCL9-mediated neutrophil recruitment to the skin. Furthermore, depleting neutrophils prevented the development of severe HSV-1 skin lesions in Ifnlr1-/- mice. Altogether, our results suggest that IFN-λ plays an immunomodulatory role in the skin that restricts neutrophil-mediated pathology during HSV infection, and suggest potential applications for IFN-λ in treating viral skin infections.

2023-09-12 | GSE242170 | GEO

IFN-λ signaling protects mice from severe HSV-1 skin disease I

2023-09-12 | GSE242068 | GEO

Nanoparticle exposure of persistently herpesvirus-infected cells reactivates latent virus and restores a signature observed during acute virus infection in vitro and in vivo

Project description:Both inhalation of environmental (nano)particles (NP) and persistent herpesvirus-infection have been implicated to contribute to the development of chronic lung disease. We hypothesized that the combination of NP exposure and virus infection leads to a different outcome than each factor alone. To test this hypothesis, we applied different carbonaceous NP in the model system of murine gammaherpesvirus 68 (MHV-68), which serves as a small animal model for gammaherpesvirus pathogenesis in vitro and in vivo. NP exposure of latently infected cells induced lytic virus production, while virus growth after de novo infection was not affected. To investigate the effect of pulmonary NP exposure in vivo, latently infected mice were instilled with carbonaceous NP or left untreated. After 24 hours, lung tissue was harvested for analysis. Immunohistochemistry demonstrated an increase in lytic viral proteins after exposure to NP. Simultaneously, gene expression analysis revealed a signature with considerable parallels to the one seen during acute infection. Analysis of the metabolome demonstrated an enrichment of phospholipids in latently infected mice after short-time exposure to NP, matching profoundly with the pattern observed during acute virus infection. Furthermore, the effect of NP exposure on virus reactivation could also be observed in human cells latently infected with Epstein-Barr-Virus (EBV). Our results indicate that the combination of NP exposure and persistent herpesvirus infection restores a molecular signature found in acute virus infection, boosts production of lytic viral proteins, and induces an inflammatory response in the lung – a pattern which might finally result in tissue damage and fibrotic alterations.

2016-12-19 | GSE79501 | GEO

Lung emphysema can be elicited by nanoparticle triggered, p38 MAPK mediated virus reactivation

Project description:Environmental particle inhalation and persistent herpesvirus infection are omnipresent and associated with chronic lung diseases. Previously, we showed that pulmonary exposure to soot-like carbonaceous nanoparticles (CNP) or fibre-shaped engineered double-walled carbon nanotubes (DWCNT) induced an increase of lytic virus protein expression in latently murine gammaherpesvirus 68 (MHV-68) infected mouse lungs, with a similar pattern as acute infection suggesting virus reactivation. However, the molecular mechanisms underlying herpesvirus reactivation as well as herpesvirus reactivation associated disease exacerbation caused by particle exposure remain unclear. Here, we investigated the effects of environmental relevant repeated particle exposure and herpesvirus reactivation mechanistically, and therapeutically. In the MHV-68 mouse model, we identified elevated lung inflammation and emphysema-like injury after repetitive CNP exposure. We further uncovered that CNP reactivated latent herpesvirus mainly in CD11b+ macrophages. Mechanistically, ERK1/2, JNK and p38 MAPK were rapidly activated after CNP and DWCNT exposure in persistently MHV-68 infected bone marrow-derived macrophages, followed by upregulation of viral gene expression and increased viral titer but without generating a pro-inflammatory transcriptional signature. Pharmacological inhibition of p38 activation abrogated CNP but not DWCNT triggered virus reactivation. In vivo, p38 inhibitor pretreatment of latently infected mice also attenuated CNP exposure induced MHV-68 reactivation. Our findings suggest that particle pollution is an environmental challenge to trigger herpesvirus reactivation and related chronic lung disease by activating latent herpesvirus via p38 MAPK dependent signalling. Pharmacological p38 inhibition might serve as a protective target to alleviate particle exposure related chronic lung disease exacerbations.

2023-09-29 | GSE223818 | GEO

Stacking the odds: multiple sites for HSV-1 latency

Project description:investigated the possible contribution of various cells (i.e., B cells, DCs, fibroblasts, glial cells, ILCs, macrophages, microglia, monocytes, NK cells, neurons, neutrophils, and T cells) isolated from TG of latently infected mice to HSV-1 latency

2023-02-22 | GSE225839 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data