Proteomic landscape of Japanese encephalitis virus-infected fibroblasts

2021 ◽  
Vol 102 (9) ◽  
Author(s):  
Kiran Bala Sharma ◽  
Simran Chhabra ◽  
Suruchi Aggarwal ◽  
Aarti Tripathi ◽  
Arup Banerjee ◽  
...  
Keyword(s):  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Protein Composition ◽  
Enrichment Analysis ◽  
Mouse Embryonic Fibroblast ◽  
Encephalitis Virus ◽  
Innate Immune ◽  
Pathway Enrichment Analysis ◽  
Interferon Stimulated Genes ◽  
Immune Sensing

Advances in proteomics have enabled a comprehensive understanding of host–pathogen interactions. Here we have characterized Japanese encephalitis virus (JEV) infection-driven changes in the mouse embryonic fibroblast (MEF) proteome. Through tandem mass tagging (TMT)-based mass spectrometry, we describe changes in 7.85 % of the identified proteome due to JEV infection. Pathway enrichment analysis showed that proteins involved in innate immune sensing, interferon responses and inflammation were the major upregulated group, along with the immunoproteasome and poly ADP-ribosylation proteins. Functional validation of several upregulated anti-viral innate immune proteins, including an active cGAS–STING axis, was performed. Through siRNA depletion, we describe a crucial role of the DNA sensor cGAS in restricting JEV replication. Further, many interferon-stimulated genes (ISGs) were observed to be induced in infected cells. We also observed activation of TLR2 and inhibition of TLR2 signalling using TLR1/2 inhibitor CU-CPT22-blocked production of inflammatory cytokines IL6 and TNF-α from virus-infected N9 microglial cells. The major proteins that were downregulated by infection were involved in cell adhesion (collagens), transport (solute carrier and ATP-binding cassette transporters), sterol and lipid biosynthesis. Several collagens were found to be transcriptionally downregulated in infected MEFs and mouse brain. Collectively, our data provide a bird’s-eye view into how fibroblast protein composition is rewired following JEV infection.

scholarly journals NS1′ of Flaviviruses in the Japanese Encephalitis Virus Serogroup Is a Product of Ribosomal Frameshifting and Plays a Role in Viral Neuroinvasiveness

2009 ◽  
Vol 84 (3) ◽  
pp. 1641-1647 ◽  
Author(s):  
Ezequiel Balmori Melian ◽  
Edward Hinzman ◽  
Tomoko Nagasaki ◽  
Andrew E. Firth ◽  
Norma M. Wills ◽  
...  
Keyword(s):  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Nonstructural Protein ◽  
Infectious Clone ◽  
Encephalitis Virus ◽  
Innate Immune ◽  
Site Directed Mutagenesis ◽  
Sequence Elements ◽  
Rna Pseudoknot ◽  
Frameshift Event

ABSTRACT Flavivirus NS1 is a nonstructural protein involved in virus replication and regulation of the innate immune response. Interestingly, a larger NS1-related protein, NS1′, is often detected during infection with the members of the Japanese encephalitis virus serogroup of flaviviruses. However, how NS1′ is made and what role it performs in the viral life cycle have not been determined. Here we provide experimental evidence that NS1′ is the product of a −1 ribosomal frameshift event that occurs at a conserved slippery heptanucleotide motif located near the beginning of the NS2A gene and is stimulated by a downstream RNA pseudoknot structure. Using site-directed mutagenesis of these sequence elements in an infectious clone of the Kunjin subtype of West Nile virus, we demonstrate that NS1′ plays a role in viral neuroinvasiveness.

scholarly journals Drug Repurposing for Japanese Encephalitis Virus Infection by Systems Biology Methods

2018 ◽  
Author(s):  
Bo-Min Lv ◽  
Xin-Yu Tong ◽  
Yuan Quan ◽  
Meng-Yuan Liu ◽  
Qing-Ye Zhang ◽  
...  
Keyword(s):  
Systems Biology ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Antiviral Agents ◽  
Drug Repurposing ◽  
Enrichment Analysis ◽  
Potential Effect ◽  
Encephalitis Virus ◽  
Mice Model ◽  
Japanese Encephalitis Virus Infection

Japanese encephalitis is a zoonotic disease caused by Japanese encephalitis virus (JEV). It is mainly epidemic in Asia with an estimated 69,000 cases occurring per year. However, no approved agents are available for the treatment of JEV infection, and existing vaccines cannot resist various types of JEV strains. Drug repurposing is a new concept for finding new indication of existing drugs, and recently, it has been used to discover new antiviral agents. Identifying host proteins involved in the progress of JEV infection and using these proteins as targets are the center of drug repurposing for JEV infection. In this study, based on the gene expression data of JEV infection and the phenome-wide association study (PheWAS) data, we identified 286 genes participating in the progress of JEV infection using the systems biology methods. The enrichment analysis of these genes suggested that the genes identified by our methods were predominantly related to viral infection pathways and immune response-related pathways. We found that bortezomib which can target these genes may have potential effect on the treatment of JEV infection. Subsequently, we evaluated the antiviral activity of bortezomib using the JEV-infected mice model. The results showed that bortezomib can lower JEV-induced lethality in mice, alleviate suffering in JEV-infected mice and reduce the damage in brains caused by JEV infection. This work provides a new method for the development of antiviral agents.

scholarly journals Drug Repurposing for Japanese Encephalitis Virus Infection by Systems Biology Methods

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3346 ◽  
Author(s):  
Bo-Min Lv ◽  
Xin-Yu Tong ◽  
Yuan Quan ◽  
Meng-Yuan Liu ◽  
Qing-Ye Zhang ◽  
...  
Keyword(s):  
Systems Biology ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Antiviral Agents ◽  
Drug Repurposing ◽  
Enrichment Analysis ◽  
Encephalitis Virus ◽  
Host Proteins ◽  
Japanese Encephalitis Virus Infection ◽  
Infection Pathways

Japanese encephalitis is a zoonotic disease caused by the Japanese encephalitis virus (JEV). It is mainly epidemic in Asia with an estimated 69,000 cases occurring per year. However, no approved agents are available for the treatment of JEV infection, and existing vaccines cannot control various types of JEV strains. Drug repurposing is a new concept for finding new indication of existing drugs, and, recently, the concept has been used to discover new antiviral agents. Identifying host proteins involved in the progress of JEV infection and using these proteins as targets are the center of drug repurposing for JEV infection. In this study, based on the gene expression data of JEV infection and the phenome-wide association study (PheWAS) data, we identified 286 genes that participate in the progress of JEV infection using systems biology methods. The enrichment analysis of these genes suggested that the genes identified by our methods were predominantly related to viral infection pathways and immune response-related pathways. We found that bortezomib, which can target these genes, may have an effect on the treatment of JEV infection. Subsequently, we evaluated the antiviral activity of bortezomib using a JEV-infected mouse model. The results showed that bortezomib can lower JEV-induced lethality in mice, alleviate suffering in JEV-infected mice and reduce the damage in brains caused by JEV infection. This work provides an agent with new indication to treat JEV infection.

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