Interleukin 27, Similar to Interferons, Modulates Gene Expression of Tripartite Motif (TRIM) Family Members and Interferes with Mayaro Virus Replication in Human Macrophages

Viruses, Год журнала: 2024, Номер 16(6), С. 996 - 996

Опубликована: Июнь 20, 2024

Background: The Tripartite motif (TRIM) family includes more than 80 distinct human genes. Their function has been implicated in regulating important cellular processes, including intracellular signaling, transcription, autophagy, and innate immunity. During viral infections, macrophages are key components of immunity that produce interferons (IFNs) IL27. We recently published IL27 IFNs induce transcriptional changes various genes, those involved JAK-STAT signaling. Furthermore, share proinflammatory antiviral pathways monocyte-derived (MDMs), resulting both common unique expression inflammatory factors IFN-stimulated genes (ISGs) encoding proteins. Interestingly, many TRIM proteins have recognized as ISGs recent years. Although it is already very well described induced by IFNs, not fully understood whether Therefore, this study, we examined the effect stimulation with type I, II, III on mRNA profiles MDMs. Methods: used bulk RNA-seq to examine profile MDMs treated or Initially, characterized patterns different subfamilies using a heatmap. Subsequently, volcano plot was employed identify commonly differentially expressed Additionally, conducted gene ontology analysis ClueGO explore biological processes regulated TRIMs, created gene-gene interaction network GeneMANIA, protein-protein interactions STRING database. Finally, data validated RT-qPCR. Mayaro virus replication also evaluated. Results: found IL27, similar upregulates several genes’ macrophages. Specifically, identified three (TRIM19, 21, 22) all types IFNs. performed first report regulation TRIM19, 22, 69 response TRIMs broad range defense viruses, life cycle regulation, negative processes. In addition, observed decrease previously Conclusions: Our results show like modulates TRIM-family members induction an response. functional demonstrated that, IFN, reduced This implies similarities at level. Moreover, identifying groups their differential expressions provides new insights into regulatory mechanisms underlying

Язык: Английский

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FSTL1 and TLR4 interact with PEDV structural proteins to promote virus adsorption to host cells

Journal of Virology, Год журнала: 2024, Номер 99(1)

Опубликована: Дек. 13, 2024

Infection with porcine epidemic diarrhea virus (PEDV) results in enormous economic damage to the global swine industry. PEDV starts its life cycle by binding receptors of host cells and adsorbing onto cellular surfaces. However, it is still unknown how adsorbs surface mechanism beneath interplay cell transmembrane protein proteins. FSTL1, which a secreted glycoprotein, participates diverse pathological physiological processes, including immune modulation proliferation differentiation. The protein, TLR4, serves as pattern recognition receptor recognizing broad spectrum pathogens, exerts crucial effect on system. In this study, we identified that FSTL1 promoted infection. Further studies demonstrated interactive relationship between structural proteins (N S2). addition, also confirmed TLR4 interacted N, S1, S2 surface. Moreover, interaction induced viral adsorption cells. This study offers explicit evidence act mediators for interacting N/S proteins.IMPORTANCEAs highly infectious (PEDV)-induced intestinal condition swine, (PED) 100% death rate among suckling piglets poses serious burden farming. Therefore, essential investigate infection, replication, proliferation. Virus begins remains unclear revealed N proteins, while (N, thoroughly methodically was engaged internalization attachment processes promoting N\S

Язык: Английский

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Construction, Identification and Analysis of the Interaction Network of African Swine Fever Virus MGF360-9L with Host Proteins

Viruses, Год журнала: 2021, Номер 13(9), С. 1804 - 1804

Опубликована: Сен. 10, 2021

African swine fever virus (ASFV) is prevalent in many countries and a contagious lethal that infects pigs, posing threat to the global pig industry public health. The interaction between host key unlocking mystery behind viral pathogenesis. A comprehensive understanding of protein may provide clues for developing new antiviral strategies. Here, we show network ASFV MGF360-9L interactions porcine kidney (PK-15) cells. Overall, 268 proteins interact with are identified using immunoprecipitation liquid chromatography–mass spectrometry (LC-MS). Accordingly, gene ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analyses were conducted, protein–protein (PPI) was created. It speculated cellular interacting involved binding, metabolism, innate immune response. Proteasome subunit alpha type (PSMA3), 26S protease regulatory 4 (PSMC1), autophagy beclin 1 regulator (AMBRA1), DEAD-box helicase 20 (DDX20) could vitro. PSMA3 PSMC1 overexpression significantly promoted replication, maintained transcriptional level PSMC1. elucidate virus–host network, which effectively provides useful protein-related information can enable further study potential mechanism pathogenesis infection.

Язык: Английский

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Porcine TRIM21 Enhances Porcine Circovirus 2 Infection and Host Immune Responses, But Inhibits Apoptosis of PCV2-Infected Cells

Viruses, Год журнала: 2022, Номер 14(1), С. 156 - 156

Опубликована: Янв. 15, 2022

Tripartite motif protein 21 (TRIM21) is an interferon-inducible E3 ligase, containing one RING finger domain, B-box motif, coiled-coil domain at the N-terminal, as well PRY and SPRY C-terminal. TRIM21 expressed in many tissues plays important role systemic autoimmunity. However, different roles virus infections. In this study, we evaluate relationship between porcine PCV2 infection host immune responses. We found that modulated expression of TRIM21. can enhance interferons proinflammatory factors decrease cellular apoptosis PCV2-infected cells. These results indicate a critical enhancing infection, which promising target for controlling developing treatment infection.

Язык: Английский

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Inhibition of DDX6 enhances autophagy and alleviates endoplasmic reticulum stress in Vero cells under PEDV infection

Veterinary Microbiology, Год журнала: 2022, Номер 266, С. 109350 - 109350

Опубликована: Янв. 21, 2022

Язык: Английский

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Mechanisms of host type I interferon response modulation by the nucleocapsid proteins of alpha- and betacoronaviruses

Archives of Virology, Год журнала: 2022, Номер 167(10), С. 1925 - 1930

Опубликована: Июнь 28, 2022

Язык: Английский

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Regulation of Tripartite Motif-Containing Proteins on Immune Response and Viral Evasion

Frontiers in Microbiology, Год журнала: 2021, Номер 12

Опубликована: Дек. 1, 2021

Tripartite motif-containing proteins (TRIMs), exhibiting ubiquitin E3 ligase activity, are involved in regulation of not only autophagy and apoptosis but also pyrotosis antiviral immune responses host cells. TRIMs play important roles modulating signaling pathways via type I interferon, NF-κB, Janus kinase/signal transducer activator transcription (JAK/STAT), Nrf2. However, viruses able to antagonize TRIM activity or evenly utilize for viral replication. This communication presents the current understanding exploited by evade response.

Язык: Английский

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The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry

Viruses, Год журнала: 2023, Номер 15(10), С. 2001 - 2001

Опубликована: Сен. 26, 2023

Although the involvement of ubiquitin-proteasome system (UPS) in several coronavirus-productive infections has been reported, whether UPS is required for infectious bronchitis virus (IBV) and porcine epidemic diarrhea (PEDV) unclear. In this study, role IBV PEDV life cycles was investigated. When suppressed by pharmacological inhibition at early infection stage, infectivity were severely impaired. Further study showed that did not change internalization particles; however, using R18 DiOC-labeled particles, we found prevented membrane fusion with late endosomes or lysosomes. addition, proteasome inhibitors blocked degradation incoming viral protein N, suggesting uncoating process genomic RNA release suppressed. Subsequently, initial translation blocked. Thus, may target virus-cellular to facilitate viruses from lysosomes, subsequently blocking following uncoating, translation, replication events. Similar observation inhibitors, ubiquitin-activating enzyme E1 inhibitor PYR-41 also impaired entry IBV, enhanced accumulation ubiquitinated proteins, depleted mono-ubiquitin. all, reveals an important coronavirus preventing identifies as a potential developing antiviral therapies coronavirus.

Язык: Английский

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The Network of Interactions between the Porcine Epidemic Diarrhea Virus Nucleocapsid and Host Cellular Proteins

Viruses, Год журнала: 2022, Номер 14(10), С. 2269 - 2269

Опубликована: Окт. 16, 2022

Host–virus protein interactions are critical for intracellular viral propagation. Understanding the between cellular and proteins may help us develop new antiviral strategies. Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe damage to global swine industry. Here, we employed co-immunoprecipitation liquid chromatography-mass spectrometry characterize 426 unique PEDV nucleocapsid (N) protein-binding in infected Vero cells. A protein–protein interaction network (PPI) was created, gene ontology (GO) annotation Kyoto Encyclopedia of Genes Genomes (KEGG) database analyses revealed N-bound belong different pathways, such as nucleic acid binding, ribonucleoprotein complex RNA methyltransferase, polymerase activities. Interactions N with 11 putative proteins: tripartite motif containing 21, DEAD-box helicase 24, G3BP stress granule assembly factor 1, heat shock family member 8, 90 alpha class B YTH domain nucleolin, Y-box binding vimentin, heterogeneous nuclear A2/B1, karyopherin subunit were further confirmed by vitro assay. In summary, studying an can facilitate identification therapeutic strategies novel targets infection.

Язык: Английский

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Adenovirus vector-mediated single chain variable fragments target the nucleocapsid protein of porcine epidemic diarrhea virus and protect against viral infection in piglets

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Янв. 24, 2023

Porcine epidemic diarrhea virus (PEDV) mainly infects the intestinal epithelial cells of pigs, causing porcine (PED). In particular, causes severe diarrhea, dehydration, and death in neonatal piglets. Maternal immunity effectively protects piglets from PEDV infection; however, maternal antibodies can only prevent attachment entry into target cells, but have no effects on intracellular viruses. Intracellular targeting virus-encoded proteins are effective preventing viral infection. We previously identified four single chain variable fragments (scFvs), ZW1-16, ZW3-21, ZW1-41, ZW4-16, which specifically targeted N protein significantly inhibited replication up-regulated interferon-λ1 (IFN-λ1) expression host cells. our current study, scFvs were subcloned replication-defective adenovirus vectors to generate recombinant adenoviruses rAdV-ZW1-16, rAdV-ZW3-21, rAdV-ZW1-41, rAdV-ZW4-16. ScFvs successfully expressed Human Embryonic Kidney 293 (HEK293) cell line J2 (IPEC-J2) biosafe for as indicated by body temperature weight, scFv excretion feces, IFN-γ interleukin-4 (IL-4) jejunum, pathological changes tissue after oral administration. Western blotting, immunofluorescence, immunohistochemical analyses showed that jejunum. The prophylactic rAdV-ZW, a cocktail rAdV-scFvs, piglet caused was investigated. Clinical symptoms orally challenged with PEDV, following two-time treatment reduced when compared PEDV-infected treated phosphate buffered saline (PBS) or rAdV-wild-type. Also, jejunal lesions observed. ScFv co-localization vivo also Next, pro-inflammatory serum cytokines such tumor necrosis factor-α (TNF-α), IL-6, IL-8, IL-12, IFN-λ assessed enzyme-linked immunosorbent assay (ELISA), suppressed PEDV-induced cytokine restored PEDV-inhibited expression. Therefore, study supported promising role treat

Язык: Английский

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