Unveiling the Role of Protein Kinase C θ in Porcine Epidemic Diarrhea Virus Replication: Insights from Genome-Wide CRISPR/Cas9 Library Screening.

Int J Mol Sci

Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Qishan Campus, Fujian Normal University, Fuzhou 350117, China.

Published: March 2024

AI Article Synopsis

  • Porcine epidemic diarrhea virus (PEDV) causes severe gastrointestinal issues in piglets and this study aimed to explore the genetic factors involved in its infection.
  • The research identified Protein kinase C θ (PKCθ) as a critical host factor for PEDV infection and found that human embryonic kidney (HEK) 293T and L929 cells are more effective for studying the virus compared to Vero and IPEC-J2 cells.
  • The study highlights the role of PKCθ in facilitating PEDV replication and suggests potential therapeutic strategies for combating PEDV infections.

Article Abstract

Porcine epidemic diarrhea virus (PEDV), a member of the Alpha-coronavirus genus in the Coronaviridae family, induces acute diarrhea, vomiting, and dehydration in neonatal piglets. This study aimed to investigate the genetic dependencies of PEDV and identify potential therapeutic targets by using a single-guide RNA (sgRNA) lentiviral library to screen host factors required for PEDV infection. Protein kinase C θ (PKCθ), a calcium-independent member of the PKC family localized in the cell membrane, was found to be a crucial host factor in PEDV infection. The investigation of PEDV infection was limited in Vero and porcine epithelial cell-jejunum 2 (IPEC-J2) due to defective interferon production in Vero and the poor replication of PEDV in IPEC-J2. Therefore, identifying suitable cells for PEDV investigation is crucial. The findings of this study reveal that human embryonic kidney (HEK) 293T and L929 cells, but not Vero and IPEC-J2 cells, were suitable for investigating PEDV infection. PKCθ played a significant role in endocytosis and the replication of PEDV, and PEDV regulated the expression and phosphorylation of PKCθ. Apoptosis was found to be involved in PEDV replication, as the virus activated the PKCθ-B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) axis in HEK293T and L929 cells to increase viral endocytosis and replication via mitochondrial apoptosis. This study demonstrated the suitability of HEK293T and L929 cells for investigating PEDV infection and identified PKCθ as a host factor essential for PEDV infection. These findings provide valuable insights for the development of strategies and drug targets for PEDV infection.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10969977PMC
http://dx.doi.org/10.3390/ijms25063096DOI Listing

Publication Analysis

Top Keywords

pedv infection
28
pedv
14
l929 cells
12
protein kinase
8
porcine epidemic
8
epidemic diarrhea
8
diarrhea virus
8
host factor
8
replication pedv
8
investigating pedv
8

Similar Publications

Porcine epidemic diarrhea virus (PEDV) is a significant pathogen affecting swine, causing severe economic losses worldwide. This study explores the regulatory role of miRNA-328-3p to ZO-1 expression and its impact on PEDV proliferation via the PLC-β1-PKC pathway in IPEC-J2 cells. We found that miRNA-328-3p can target ZO-1, influencing its expression and subsequently affecting the integrity of tight junctions in the cells.

View Article and Find Full Text PDF

Traditional Chinese medicine has unique advantages in preventing and treating COVID-19, and Fuzheng Jiedu decoction (FZJDD) was reported to be effective against COVID-19 in clinical trials. To investigate the potential mechanisms and material basis of FZJDD against SARS-CoV-2, we performed SARS-CoV-2 target protein inhibition analyses and a metabolite full spectrum analysis of FZJDD. Interestingly, FZJDD was found to block the binding of SARS-CoV-2 Spike protein with the receptor ACE2 and inhibit the activity of SARS-CoV-2 3CLpro.

View Article and Find Full Text PDF

Development of a capsid protein-based ELISA for the detection of PCV2 antibodies in swine serum.

Pol J Vet Sci

December 2024

Key Laboratory of Animal Pathogen and Biosafety Education of the Ministry of Education, Zhengzhou 450000, China.

Porcine circovirus type 2 (PCV2) is the major causative agent of postweaning multisystemic wasting syndrome which leads to significant economic losses in the global swine industry. In China, there is a widespread dissemination of PCV2 infection in the pig population. Serological diagnosis of the disease is considered as an effective control measure.

View Article and Find Full Text PDF

PEDV is a highly contagious enteric pathogen that can cause severe diarrhea and death in neonatal pigs. Despite extensive research, the molecular mechanisms of host's response to PEDV infection remain unclear. In this study, differentially expressed genes (DEGs), time-specific coexpression modules, and key regulatory genes associated with PEDV infection were identified.

View Article and Find Full Text PDF

Porcine epidemic diarrhea virus (PEDV) induces enteritis and diarrhea in piglets. Mitochondrial DNA (mtDNA) contributes to virus-induced inflammatory responses; however, the involvement of inflammasomes in PEDV infection responses remains unclear. We investigated the mechanism underlying inflammasome-mediated interleukin (IL)-1β secretion during the PEDV infection of porcine intestinal epithelial (IPEC-J2) cells.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!