The Insufficient Activation of RIG-I–Like Signaling Pathway Contributes to Highly Efficient Replication of Porcine Picornaviruses in IBRS-2 Cells

Autor: Weijun Cao, Xiangle Zhang, Kangli Li, Shuying Chen, Shasha Li, Yi Ru, Zixiang Zhu, Zheng Haixue, Xiangtao Liu, Fan Yang
Rok vydání: 2021
Předmět:
Swine
Picornaviridae
Virus Replication
RIG-I–like receptor signaling pathway
antiviral response
JAK-STAT
Janus kinase signal transducer and activator of transcription
Interferon
MDA5
melanoma differentiation–associated protein 5
Receptors
Immunologic
IL-6
interleukin-6
MOI
multiplicity of infection
DMEM
Dulbecco's modified Eagle's medium
IRF7
IFN regulatory factor 7
JAK-STAT signaling pathway
SVV
Seneca Valley virus
interferon
iTRAQ
isobaric tag for relative and absolute quantitation
TCID50
50% tissue culture infective dose
General Medicine
senecavirus A
Cell biology
CPE
cytopathic effect
DEAD Box Protein 58
IBRS-2
Instituto Biologico-Rim Suino-2
Signal Transduction
medicine.drug
IRF3
IFN regulatory factor 3
FDR
false discovery rate
RLR
RIG-I–like receptor
MAVS
mitochondrial antiviral-signaling protein
PK-15
porcine kidney-15 cells
Biology
RIG-I-like receptor
KEGG
Kyoto Encyclopedia of Genes and Genomes
Cell Line
FBS
fetal bovine serum
GO
Gene Ontology
medicine
Animals
ISG
interferon-stimulated gene
IFN
interferon
hpi
hours post infection
Picornaviridae Infections
Innate immune system
foot-and-mouth disease virus
Research
CDS
coding sequence
ACN
acetonitrile
RIG-I
retinoic acid–inducible gene I
Oncolytic virus
SeV
Sendai virus
DEP
differentially expressed protein
TBK1
TANK-binding kinase 1
FMDV
foot-and-mouth disease virus
qPCR
quantitative PCR
RIG-I-Like Receptor Signaling Pathway
IRF3
Janus kinase
HA
hemagglutinin
Zdroj: Molecular & Cellular Proteomics : MCP
ISSN: 1535-9476
DOI: 10.1016/j.mcpro.2021.100147
Popis: Seneca Valley virus (SVV) or commonly known as senecavirus A, is one of the picornavirus that is associated with vesicular disease and neonatal mortality in swine herds. Our previous study found that SVV replicates extremely faster in porcine Instituto Biologico-Rim Suino-2 (IBRS-2) cells than that in porcine kidney-15 (PK-15) cells. However, the underlying mechanism remains unknown. In this study, we comprehensively compared the expression features between IBRS-2 cells and PK-15 cells in response to SVV infection by an unbiased high-throughput quantitative proteomic analysis. We found that the innate immune response–related pathways were efficiently activated in PK-15 cells but not in IBRS-2 cells during SVV infection. A large amount of interferon (IFN)-stimulated genes were induced in PK-15 cells. In contrast, no IFN-stimulated genes were induced in IBRS-2 cells. Besides, we determined similar results in the two cell lines infected by another porcine picornavirus foot-and-mouth disease virus. Further study demonstrated that the Janus kinase signal transducer and activator of transcription signaling pathway was functioning properly in both IBRS-2 and PK-15 cells. A systematic screening study revealed that the aberrant signal transduction from TANK-binding kinase 1 to IFN regulatory factor 3 in the retinoic acid–inducible gene I–like receptor signaling pathway in IBRS-2 cells was the fundamental cause of the different innate immune response manifestation and different viral replication rate in the two cell lines. Together, our findings determined the different features of IBRS-2 and PK-15 cell lines, which will help for clarification of the pathogenesis of SVV. Besides, identification of the underlying mechanisms will provide new targets and an insight for decreasing the viral clearance rate and probably improve the oncolytic effect by SVV in cancer cells.
Graphical Abstract
Highlights • Divergent innate immune responses were triggered by SVV in IBRS-2 and PK-15 cells. • SVV induced higher levels of type I IFN in PK-15 cells than in IBRS-2 cells. • IBRS-2 cell line has an aberrant RLR pathway but an intact type I IFN pathway. • TBK1-mediated antiviral signal transduction was dysfunctional in IBRS-2 cells.
In Brief Both IBRS-2 and PK-15 cells have been widely used for porcine picornavirus research. However, the virus replicates faster and causes severer CPE in IBRS-2 cells than in PK-15 cells, and the underlying mechanism remains unknown. Proteomic analyses suggested that the RLR pathway was in a dysfunctional state in IBRS-2 cells. We finally determined that the disabled signal transduction from TBK1 to IRF3 in IBRS-2 cells was the fundamental cause of dysfunction of the RLR pathway during porcine picornavirus infection.
Databáze: OpenAIRE
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