Sequence diversity of CV777 PEDV strains
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ABSTRACT:
PROVIDER: PRJEB20818 | ENA |
REPOSITORIES: ENA
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Project description:Porcine epidemic diarrhea virus (PEDV) is a highly contagious virus that poses a serious threat to the global pig industry. Despite extensive research efforts, the functional receptor for PEDV remains unclear. In this study, we identified susceptible and non-susceptible cell lines to PEDV infection, and performed RNA-seq analysis on these cell lines. Using Weighted Gene Co-expression Network Analysis (WGCNA), we have identified the key pathways that correlated with the PEDV entry pathway. We found that cholesterol, sterols, and lipid transport and homeostasis were strongly correlated with PEDV entry, suggesting a potential role for cholesterol in PEDV entry. We then treated susceptible cell lines with a cholesterol transport inhibitor and found that inhibition of cholesterol transport could significantly inhibit PEDV entry in these cells. Together, our results suggest that cholesterol transport may play a critical role in the entry of PEDV into susceptible cells, and that targeting cholesterol transport may represent a potential strategy for controlling PEDV transmission. Our findings provide new insights into the mechanism of PEDV entry and may pave the way for the development of new therapeutic strategies against this economically important virus. Further studies are warranted to elucidate the detailed mechanism of PEDV entry, and to explore the potential of cholesterol transport inhibitors as a means of controlling PEDV transmission.
2023-07-06 | GSE236338 | GEO
Project description:Swine coronavirus-porcine epidemic diarrhea virus (PEDV) with specific susceptibility to pigs has existed for decades, and recurrent epidemics caused by mutant strains have swept the world again since 2010. Here, single-cell RNA-sequencing was used to perform a systematic analysis of pig small intestines infected with PEDV for the first time. Multiple cell types were identified by representative markers, including the unique marker DNAH11 of tuft cells. Meanwhile, the goblet and tuft cells were also susceptible to PEDV except enterocytes. PEDV infection obviously upregulated REG3G, which significantly inhibited virus replication. Notably, IFN-DELTAs in goblet and enterocyte progenitor cells were increased in virus infected piglet, and IFN-DELTA5 could induce GBP1, ISG15, OAS2 and IFITM1 dramatically raised in IPEC-J2 cells and restricted PEDV replication. Complement molecules were mainly expressed in intestinal cells excepting tuft cells, but PEDV decreased C3, C4A, and C5 in enterocytes, thus escaping the antiviral effect of C3. Finally, enterocytes expressed almost all coronavirus entry factors, and PEDV infection caused significant upregulation of the coronavirus receptor ACE2 in porcine enterocyte cells. In summary, this study systematically studied the response of different cell types in small intestine of pigs after PEDV infection, which deepened the understanding of viral pathogenesis.
2022-04-27 | GSE175411 | GEO
Project description:Porcine epidemic diarrhea virus (PEDV) is a deadly coronavirus for neonatal piglets and no effective vaccines are available. Transcriptional regulatory sequences (TRSs) are critical in regulating coronavirus discontinuous transcription. Also, TRSs contribute to a high recombination rate of coronaviruses, leading to difficulty in developing safe live vaccines. We hypothesize that recoding the TRS core sequences (TRS-CS) of PEDV can make the recombination impossible between the engineered vaccine virus and field strains or wildtype viruses. We used an infectious clone-derived reporter PEDV, dORF3-EGFP, as the backbone to generate a remodeled TRS (RMT) mutant that carries the recoded leader and body TRS-CSs. The RMT and dORF3-EGFP showed comparable replication efficiency in Vero cells. However, the incompatibility between the rewired and wildtype TRS-CSs led to few EGFP in RMT-infected cells. Furthermore, RMT and dORF3-EGFP had a similar attenuated phenotype, replication efficiency, and protective immunogenicity in neonatal pigs. RNA sequencing analysis indicated that EGFP transcription directed by the heterogenous TRS-CSs was significantly reduced to an extremely low level. Meanwhile, recombinant viruses were not detected in Vero cells and in pigs that were co-infected with RMT and a PEDV S-INDEL strain, Iowa106. In vitro and in vivo passaging of the RMT did not result in reversion mutations in the rewired TRS-CSs, introduced gaps, and disrupted wildtype TRSs. In summary, the RMT mutant was resistant to recombination and genetically stable and can be further optimized (e.g., deletion of the EGFP) to serve as a platform to develop safe PEDV live attenuated vaccines.
2023-11-04 | GSE246991 | GEO
Project description:Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic virus that causes severe gastrointestinal disease in neonatal piglets, often leading to high mortality. To advance the study of viral pathogenesis, it is essential to develop an in vitro model that accurately replicates swine enteric coronavirus infections. In this study, we designed a porcine intestinal apical-out organoid culture system that supports viral replication while allowing for long-term culture and experimental manipulation. Using apical-out organoids derived from the duodenum, jejunum, and ileum, we examined region-specific gene expression profiles in response to PEDV infection. Bulk RNA sequencing revealed distinct gene expression patterns, highlighting the regional differences in intestinal physiology during infection. Differential gene expression analysis indicated that each intestinal segment activates specific signaling pathways related to cell survival and antiviral responses following PEDV infection. Functional analyses identified key pathways involved in cell development, signaling, apoptosis, and survival. This study elucidates the mechanisms underlying the differential responses of specific intestinal regions to PEDV, which may inform the selection of optimal models for future PEDV research. In summary, our systematic investigation into the responses of various small intestine segments following PEDV infection provides deeper insights into viral pathogenesis.
2024-12-31 | GSE280630 | GEO
Project description:Little is known about the extent of genetic variability among Entamoeba strains and potential genotypic associations with virulence. Variable phenotypes have been identified for Entamoeba strains. E. histolytica is invasive and causes colitis and liver abscesses, but only in 10% of infected individuals; 90% of subjects remain asymptomatically colonized. E. dispar, a closely related species, appears to be incapable of causing invasive disease. In order to determine the extent of genetic diversity among Entamoeba strains we have developed an E. histolytica genomic DNA microarray and used it to genotype strains of E. dispar and E. histolytica. Based on the identification of divergent genetic loci, all six strains (four EH and two ED) had unique genetic fingerprints. Genomic regions with unusually high levels of divergence were identified indicating that structural or evolutionary pressures are molding selective regions of the Entamoeba genome. Comparison of divergent genetic regions allowed us to readily distinguish between EH and ED, identify novel genetic regions that may be used for strain and species typing, and identity a number of novel potential virulence determinants. Among these are Androgen Inducible Gene1, a CXXC receptor kinase, a peroxiredoxin 1-related gene, a Ras family member gene, a Rab geranylgeranyltransferase, and a gene with a UPF0034 domain. Among the four EH strains, an avirulent strain EH (Rahman) was the most divergent and phylogenetically distinct raising the intriguing possibility that genetic subtypes of E. histolytica may be at least partially responsible for the observed variability in clinical outcomes. Our approach shows the utility of a microarray-based genotyping assay to identify genetic variability between Entamoeba isolates and can readily be applied to the study of clinical isolates. A genotyping experiment design type classifies an individual or group of individuals on the basis of alleles, haplotypes, SNP's. Keywords: genotyping_design
2005-08-26 | GSE3207 | GEO
Project description:Helicobacter pylori colonizes the stomach of half of the world's population, causing a wide spectrum of disease ranging from asymptomatic gastritis to ulcers to gastric cancer. Although the basis for these diverse clinical outcomes is not understood, more severe disease is associated with strains harboring a pathogenicity island. To characterize the genetic diversity of more and less virulent strains, we examined the genomic content of 15 H. pylori clinical isolates by using a whole genome H. pylori DNA microarray. We found that a full 22% of H. pylori genes are dispensable in one or more strains, thus defining a minimal functional core of 1281 H. pylori genes. While the core genes encode most metabolic and cellular processes, the strain-specific genes include genes unique to H. pylori, restriction modification genes, transposases, and genes encoding cell surface proteins, which may aid the bacteria under specific circumstances during their long-term infection of genetically diverse hosts. We observed distinct patterns of the strain-specific gene distribution along the chromosome, which may result from different mechanisms of gene acquisition and loss. Among the strain-specific genes, we have found a class of candidate virulence genes identified by their coinheritance with the pathogenicity island. Keywords: other
2001-07-25 | GSE6 | GEO
Project description:Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic infectious disease targeting pig intestine that is widespread in the world, causing huge economic losses to pig industry. PEDV N protein is the core protein of PEDV, which locates in the cytoplasm and wraps the RNA genome of the virus to form spiral ribonucleoprotein (RNP). However, host proteins interacting with N proteins and their role in PEDV replication have not been fully elucidated. In this study, PEDV-N labeled antibodies were immunoprecipitated (Co-IP) and combined with LC-MS/MS to screen host proteins interacting with N proteins.
2024-06-07 | PXD052564 | Pride
Project description:The genetic diversity of JEV vaccine strains SA14-14-2, SA14-5-3 and SA14-2-8 and the WT parental WT strain they were derived from, SA14, were sequenced using Illumina technology. Passages of the strains were also sequenced to observe changes in genetic diversity.
2021-01-21 | E-MTAB-9385 | biostudies-arrayexpress
Project description:Herpesviruses have a group of genes earmarked for expression late in the infection. Beta- and gammaherpesviruses utilize a six-member set of viral late transcription factors to selectively activate these genes by binding to a DNA sequence signature in gene promoters. We made an unexpected discovery that differences in sequence signature configures the late gene expression program for human cytomegalovirus, a beta-herpesvirus of global public health importance. Diversity in signature patterns expands promoter targets and pre-sets amount of individual promoter output. A unique palindromic sequence signature is linked to the activation of back-to-back promoters at multiple locations in the viral genome. We deduce that diversity in late transcription factor targets functionally orchestrates the productive rollout of the late-stage infection. This may be a generalizable feature adopted by beta- and gammaherpesvirus subfamilies.
2021-07-01 | GSE168165 | GEO