Gene expression profile of HCT-8 cells following single or co-infections with Cryptosporidium parvum and bovine coronavirus DOI Creative Commons
Alejandro Jiménez‐Meléndez, Ruchika Shakya, Turhan Markussen

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: March 23, 2023

Abstract Among the causative agents of neonatal diarrhoea in calves, two most prevalent are bovine coronavirus (BCoV) and intracellular parasite Cryptosporidium parvum . Although several studies indicate that co-infections associated with greater symptom severity, host-pathogen interplay remains unresolved. Here, our main objective was to investigate modulation transcriptome HCT-8 cells during single BCoV C. For this, were inoculated (1) alone, (2) (3) simultaneously. After 24 72 h, harvested analyzed using high-throughput RNA sequencing. Following differential expression analysis, over 6000 differentially expressed genes (DEGs) identified virus co-infected at hpi, whereas only 52 DEGs found -infected same time point. Pathway (KEGG) gene ontology (GO) analysis showed virus-infected mostly immune pathways (such as NFKβ, TNFα or, IL-17), apoptosis regulation transcription, a more limited effect exerted by observed co-infection apparently dominated virus, 800 uniquely hpi. Our findings provide insights on possible biomarkers co-infection, which could be further explored vivo models.

Language: Английский

UBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors DOI Creative Commons
Duomeng Yang, Tingting Geng, Andrew G. Harrison

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 26, 2024

Abstract The Retinoic acid-Inducible Gene I (RIG-I) like receptors (RLRs) are the major viral RNA sensors essential for initiation of antiviral immune responses. RLRs subjected to stringent transcriptional and posttranslational regulations, which ubiquitination is one most important. However, role in RLR transcription unknown. Here, we screen 375 definite ubiquitin ligase knockout cell lines identify Ubiquitin Protein Ligase E3 Component N-Recognin 5 (UBR5) as a positive regulator transcription. UBR5 deficiency reduces responses viruses, while increases replication primary cells mice. Ubr5 mice more susceptible lethal virus infection than wild type littermates. Mechanistically, mediates Lysine 63-linked Tripartite Motif 28 (TRIM28), an epigenetic repressor RLRs. This modification prevents intramolecular SUMOylation TRIM28, thus disengages TRIM28-imposed brake on In sum, enables rapid upregulation expression boost by ubiquitinating de-SUMOylating TRIM28.

Language: Английский

Citations

6
Translation—A tug of war during viral infection DOI Creative Commons
Batsheva Rozman,

Tal Fisher,

Noam Stern‐Ginossar

et al.

Molecular Cell, Journal Year: 2022, Volume and Issue: 83(3), P. 481 - 495

Published: Nov. 4, 2022

Language: Английский

Citations

26
Manganese-dependent microRNA trimming by 3′→5′ exonucleases generates 14-nucleotide or shorter tiny RNAs DOI Creative Commons
GeunYoung Sim, Audrey C. Kehling, Mi Seul Park

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(51)

Published: Dec. 12, 2022

MicroRNAs (miRNAs) are about 22-nucleotide (nt) noncoding RNAs forming the effector complexes with Argonaute (AGO) proteins to repress gene expression. Although tiny (tyRNAs) shorter than 19 nt have been found bind plant and vertebrate AGOs, their biogenesis remains a long-standing question. Here, our in vivo vitro studies show several 3′→5′ exonucleases, such as interferon-stimulated 20 kDa (ISG20), three prime repair exonuclease 1 (TREX1), ERI1 (enhanced RNAi, also known 3′hExo), capable of trimming AGO-associated full-length miRNAs 14-nt or tyRNAs. Their guide occurs manganese-dependent manner but independently sequence loaded four human AGO paralogs. We that ISG20-mediated makes Argonaute3 (AGO3) slicer. Given high Mn 2+ concentrations stressed cells, virus-infected neurodegeneration, study sheds light on roles -dependent exonucleases remodeling silencing.

Language: Английский

Citations

24
Intracellular Host Restriction of Hepatitis B Virus Replication DOI Creative Commons
Prakriti Sinha, Chloe L. Thio, Ashwin Balagopal

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(5), P. 764 - 764

Published: May 11, 2024

The hepatitis B virus (HBV) infects hepatocytes and hijacks host cellular mechanisms for its replication. Host proteins can be frontline effectors of the cell’s defense restrict viral replication by impeding multiple steps during intracellular lifecycle. This review summarizes many well-described restriction factors, their restriction, counteractive measures HBV, with a special focus on transcription. We discuss some limitations knowledge gaps about highlighting how these factors may harnessed to facilitate therapeutic strategies against HBV.

Language: Английский

Citations

4
TGF β1 promotes the polarization of M2-type macrophages and activates PI3K/mTOR signaling pathway by inhibiting ISG20 to sensitize ovarian cancer to cisplatin DOI
Jianfa Wu, Lingli Jiang, Sihong Wang

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 134, P. 112235 - 112235

Published: May 17, 2024

Language: Английский

Citations

4
Internal RNA 2′O-methylation in the HIV-1 genome counteracts ISG20 nuclease-mediated antiviral effect DOI Creative Commons
Priscila El Kazzi, Nadia Rabah, Célia Chamontin

et al.

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 51(6), P. 2501 - 2515

Published: Nov. 10, 2022

Abstract RNA 2′O-methylation is a ‘self’ epitranscriptomic modification allowing discrimination between host and pathogen. Indeed, human immunodeficiency virus 1 (HIV-1) induces of its genome by recruiting the cellular FTSJ3 methyltransferase, thereby impairing detection RIG-like receptors. Here, we show that 2′O-methylations interfere with antiviral activity interferon-stimulated gene 20-kDa protein (ISG20). Biochemical experiments showed ISG20-mediated degradation 2′O-methylated pauses two nucleotides upstream at methylated residue. Structure-function analysis indicated this inhibition due to steric clash ISG20 R53 D90 residues nucleotide. We confirmed hypomethylated HIV-1 genomes produced in FTSJ3-KO cells were more prone vitro than those expressing FTSJ3. Finally, found reverse-transcription was impaired T interferon-induced ISG20, demonstrating direct antagonist effect on activity.

Language: Английский

Citations

19
Transcriptomics-based investigation of resistance differences to swine fever between large white pigs and min pigs DOI Creative Commons
Jia Li,

Deming Ren,

Xiangxu Meng

et al.

Virus Research, Journal Year: 2025, Volume and Issue: 353, P. 199536 - 199536

Published: Feb. 1, 2025

The genetic foundations underlying the observed disease resistance in certain indigenous pig breeds, notably Min pigs of China, present a compelling underexplored subject study. Exploring mechanisms these breeds could lay groundwork for improvements immunity, potentially augmenting overall productivity. In this study, whole blood samples were collected from pre- and post- swine fever vaccinated Large White transcriptome sequencing. mRNA lncRNA both analyzed, intra-group inter-group comparisons also conducted. results indicated that greater number immune-related pathways such as JAK-STAT PI3K-AKT signaling enriched pigs. Furthermore, genes involved inflammation antiviral responses, including IL16, IL27, USP18, DHX58, upregulated post-vaccination compared to This heightened immune responsiveness contribute differences between

Language: Английский

Citations

0
Not all RNAs are created equal for the antiviral RNase ISG20 DOI Creative Commons
Jim Zoladek, Séverine Deymier, Andrea Cimarelli

et al.

Trends in Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

ISG20 is a broad-spectrum antiviral protein capable of specifically degrading viral RNA. Here, we examine the different strategies developed by viruses to evade ISG20-mediated restriction, shedding light on how this exonuclease distinguishes between self and non-self RNAs, highlighting many questions that remain unanswered.

Language: Английский

Citations

0
ISG20 stimulates anti-tumor immunity via a double-stranded RNA-induced interferon response in ovarian cancer DOI Creative Commons
Zhigao Chen,

Min Yin,

Haixue Jia

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: June 5, 2023

Augmentation of endogenous double-stranded RNA (dsRNA) has become a promising strategy for activating anti-tumor immunity through induction type I interferon (IFN) in the treatment ovarian carcinoma. However, underlying regulatory mechanisms dsRNA carcinoma remain elusive. From The Cancer Genome Atlas (TCGA), we downloaded expression profiles and clinical data patients with Using consensus clustering method, can be classified by their level core interferon-stimulated genes (ISGs): IFN signatures high low. group had good prognosis. Gene set enrichment analysis (GSEA) showed that differentially expressed (DEGs) were primarily associated anti-foreign immune responses. Based on results from protein-protein interaction (PPI) networks survival analysis, ISG20 was identified as key gene involved host response. Further, elevated cancer cells led to increased IFN-β production. improved immunogenicity tumor generated chemokines attract infiltrate area. Upon overexpression ISG20, accumulated cell stimulated production Retinoic acid-inducible (RIG-I)-mediated sense pathway. accumulation ribonuclease activity ISG20. This study suggests targeting is potential therapeutic approach treat cancer.

Language: Английский

Citations

9
Systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the BNT162b COVID-19 vaccine DOI Creative Commons
Ivan Odak, Lennart Riemann, Inga Sandrock

et al.

EBioMedicine, Journal Year: 2023, Volume and Issue: 99, P. 104947 - 104947

Published: Dec. 29, 2023

Human immune responses to COVID-19 vaccines display a large heterogeneity of induced immunity and the underlying mechanisms for this remain largely unknown.

Language: Английский

Citations

9