Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The lipopeptide Pam3CSK4 inhibits Rift Valley fever virus infection and protects from encephalitis

ABSTRACT: Rift Valley fever virus (RVFV) is an encephalitic bunyavirus that can infect neurons in the brain. There are no approved therapeutics that can protect from RVFV encephalitis. Innate immunity, the first line of defense against infection, canonically antagonizes viruses through interferon signaling. We found that interferons did not efficiently protect primary cortical neurons from RVFV, unlike other cell types. To identify alternative neuronal antiviral pathways, we screened innate immune ligands and discovered that the TLR2 ligand Pam3CSK4 inhibited RVFV infection, and other bunyaviruses. Mechanistically, we found that Pam3CSK4 blocks viral fusion, independent of TLR2. In a mouse model of RVFV encephalitis, Pam3CSK4 treatment protected animals from infection and mortality. Overall, Pam3CSK4 is a bunyavirus fusion inhibitor active in primary neurons and the brain, representing a new approach toward the development of treatments for encephalitic bunyavirus infections.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE241547 | GEO | 2024/06/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

MDP- and Pam3CSK4-induced genes in naïve and tolerant macrophages

2008-03-15 | GSE10182 | GEO

Temporal alterations in the HSAEC transcriptome following infection by virulent and attenuated strains of Rift Valley Fever Virus

Project description:Rift Valley fever virus (RVFV) causes major outbreaks among livestock, characterized by “abortion storms” in which spontaneous abortion occurs in almost 100% of pregnant ruminants. Humans can also become infected with mild symptoms that can progress to more severe symptoms, such as hepatitis, encephalitis, and hemorrhagic fever. The goal of this study was to use RNA-sequencing (RNA-seq) to analyze the host transcriptome in response to RVFV infection. G2/M DNA damage checkpoint, ATM signaling, mitochondrial dysfunction, regulation of the antiviral response, and integrin-linked kinase (ILK) signaling were among the top altered canonical pathways with both the attenuated MP12 strain and the fully virulent ZH548 strain. Although several mRNA transcripts were highly upregulated, an increase at the protein level was not observed for the selected genes, which was at least partially due to the NSs dependent block in mRNA export. Inhibition of ILK signaling, which is involved in cell motility and cytoskeletal reorganization, resulted in reduced RVFV replication, indicating that this pathway is important for viral replication. Overall, this is the first global transcriptomic analysis of the human host response following RVFV infection, which could give insight into novel host responses that have not yet been explored.

2017-08-11 | GSE102481 | GEO

Transcription profiling of mouse naive and tolerant macrophages treated with MDP- and Pam3CSK4

Project description:Most of the genes were self-tolerized by Pam3CSK4 and MDP but there was no or minimal cross-tolerization. The transcriptome induced via Nod2 stimulation is greatly expanded in TLR2-tolerant macrophages. Experiment Overall Design: Genes induced by Pam3CSK4 or MDP were selected based on a three-fold increase over expression levels in unstimulated macrophages. Tolerized genes are defined as genes downregulated more than 2-fold in tolerant macrophages stimulated with Pam3CSK4 or MDP.

2008-04-05 | E-GEOD-10182 | biostudies-arrayexpress

Gene expression profiling of peripheral blood and alveolar recruited mononuclear phagocytes in Pam3CSK4 treated mice

2009-01-01 | GSE11978 | GEO

Effects of Rift Valley fever virus infection on gene expression and alternative splicing in HEK 293 cells

Project description:Rift Valley fever virus (RVFV) is an important human and livestock pathogen. To better understand the molecular virology and mechanisms of pathogenesis in human HEK293 cells during RVFV MP-12 strain infection, we used high-throughput mRNA sequencing technology to identify and analyze differentially expressed genes and mRNA splicing patterns triggered by infection or by expression of RVFV nucleocapsid protein. Here we supply the results of our RNA-seq analysis of RVFV-infected cells and cells transfected with RVFV nucleocapsid protein expressing plasmids. Some of the results were published in: "Transcriptome profiling in Rift Valley fever virus infected cells reveals modified transcriptional and alternative splicing programs" by Katherine E Havranek, Luke Adam White, Jean-Marc Lanchy, J Stephen Lodmell. PLoS One. 2019 May 28;14(5):e0217497. PMID: 31136639 PMCID: PMC6538246.

2023-09-12 | GSE242551 | GEO

MF59 and Pam3CSK4 boost adaptive responses to influenza subunit vaccine through an IFN type I independent mechanism of action

Project description:Analysis of whole mouse muscle and inguinal lymph node gene expression signature induced after 6h by in-vivo intramuscularly administration of MF59, alum, CpG, resiquimod (R848), Pam3CSK4 and DMSO and PBS controls. Analysis of splenocyte gene expression signature induced by the same treatments after 6h of incubation. MF59 and alum are licensed human vaccine adjuvants; CpG is a TLR9-agonist adjuvant; resiquimod (R848) is a TLR7/8-agonist adjuvant and Pam3CSK4 is a TLR2-agonist adjuvant.

2012-02-22 | E-MTAB-942 | biostudies-arrayexpress

Microarray analysis of bone-marrow derived macrophages (BMDMs) stimulated with two different TLR2 agonists, H. hepaticus polysaccharide or Pam3CSK4

Project description:Identification of pro- and anti-inflammatory pathways induced in M-CSF differentiated bone-marrow derived macrophages (BMDMs) after 3 h stimulation with two different TLR2 agonists, Helicobacter hepaticus polysacharide and Pam3CSK4 (75 ng/ml), using TSB (Tryptone Soya Broth) medium as a control

2017-08-25 | E-MTAB-5780 | biostudies-arrayexpress

Alteration in the Culex pipiens transcriptome reveals the implication of the mosquito immune system during Rift Valley fever phlebovirus infection

Project description:Rift valley fever (RVF) is an emerging zoonotic disease and it is caused by Rift valley fever phlebovirus (RVFV). This virus is commonly transmitted in endemic areas between wild ruminants and mosquitoes, mainly by mosquitoes of Culex and Aedes genus. Starting from 2000, several outbreaks have been reported outside the African continent, in countries facing the Mediterranean Sea, such as Saudi Arabia. The available vaccines for ruminants present limited efficacy or residual pathogenic effects. Consequently, new strategies are urgently required to limit the expansion of this zoonotic virus. The main objective of this work is to investigate the molecular responses of Culex pipiens to RVFV focusing mainly on genes implicated in the classical innate immunity pathways, RNAi mechanism and apoptosis process in order to elucidate the implicated genes in viral infection. The immune altered genes here described could be potential targets to control RVFV infection in mosquitoes. Some of the genes related to the immune defense response were previously described in others mosquito-arbovirus models, as also in Drosophila and human. To our knowledge, this study elucidates for the first time the Cx. pipiens-RVFV interaction in terms of defense infection-response, which was largely under studied and provides information to develop new approaches to prevent and control the expansion of the virus in the future.

2020-11-02 | GSE142339 | GEO

Transcription profiling of mouse peripheral blood and alveolar recruited mononuclear phagocytes in Pam3CSK4 treated animals

Project description:Aim of this project was to examine the global gene expression profiles of mononuclear phagocytes recruited from peripheral blood to the alveolar space following alveolar deposition of the TLR2-ligand Pam3CSK4 in transgenic CX3CR1+/GFP mice. Experiment Overall Design: Alveolar macrophages (AM) and peripheral blood monocytes (PBM) were isolated from broncho-alveolar lavages and from blood, respectively, using FACS. Expression profiles from AM and PBM of the same mice were compared on the same slides. Each labeled RNA sample contained RNA pooled from six individuals. Four pairs of RNA from corresponding AM and PBM pools were hybridized, giving a total amount of 24 individual mice analyzed. Two hybridizations were performed with AM labeled with Cy3 and PBM with Cy5, two hybridizations were performed with swaped dyes.

2009-01-09 | E-GEOD-11978 | biostudies-arrayexpress

Human dendritic cell microRNA profile after NOD2 and / or TLR2 stimulation

Project description:microRNA expression in human monocyte-derived DCs following stimulation with NOD2 ligand MDP, TLR2 ligand Pam3CSK4, or both. 4 condition experiment with two timepoints, and 4 biological replicates. Conditions: unstimulated; MDP stimulated; Pam3CSK4 stimulated; MDP + Pam3CSK4 stimulated. Timepoints: 4 hours and 24 hours.

2013-06-01 | E-GEOD-44785 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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