Cholesterol 25-hydroxylase negatively regulates porcine intestinal coronavirus replication by the production of 25-hydroxycholesterol

Veterinary Microbiology, Год журнала: 2019, Номер 231, С. 129 - 138

Опубликована: Март 6, 2019

Язык: Английский

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RNA-Seq based transcriptome analysis during bovine viral diarrhoea virus (BVDV) infection

BMC Genomics, Год журнала: 2019, Номер 20(1)

Опубликована: Окт. 24, 2019

Abstract Background Bovine viral diarrhoea virus (BVDV) is the member of genus Pestivirus within Flaviviridae family and responsible for severe economic losses in cattle industry. BVDV can employ ‘infect-and-persist’ strategy ‘hit-and-run’ to remain associated with hosts thus contributes circulation herds. have also evolved various strategies evade innate immunity host. To further understand mechanisms by which overcomes host cell immune response provide more clues understanding BVDV-host interaction, this descriptive study, we conducted a investigation differentially expressed genes (DEGs) during infection RNA-Seq analysis. Results Our analysis identified 1297, 1732, 3072, 1877 DEGs comparison groups mock vs. MDBK cells infected post 2 h (MBV2h), MBV6h, MBV12h, MBV24h, respectively. The reproducibility repeatability results were validated RT-qPCR. Enrichment analyses GO annotations KEGG pathways revealed that are potentially induced may participate interactions. Protein-protein interaction (PPI) network potential interactions among DEGs. findings suggested upregulation involved lipid metabolism. expression antiviral roles, including ISG15 , Mx1 OSA1Y found be downregulated inhibition system infection. levels F3 C1R KNG1 CLU C3 FB SERPINA5 SERPINE1 C1S F2RL2 C2 belong complement coagulation signalling cascades, infection, might play crucial role Conclusion In our changes transcriptome profile BVDV-infection altering host’s metabolic network, proteins contributed proliferation. above provided unique insights studies on underlying

Язык: Английский

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Viral Infections and Interferons in the Development of Obesity

Biomolecules, Год журнала: 2019, Номер 9(11), С. 726 - 726

Опубликована: Ноя. 12, 2019

Obesity is now a prevalent disease worldwide and has multi-factorial etiology. Several viruses or virus-like agents including members of adenoviridae, herpesviridae, slow virus (prion), hepatitides, have been associated with obesity; meanwhile obese patients are shown to be more susceptible viral infections such as during influenza dengue epidemics. We examined the co-factorial role infections, particularly persistent cases, in synergy high-fat diet induction obesity. Antiviral interferons (IFNs), key immune regulators against autoimmunity, emerge pivotal player regulation adipogenesis. In this review, we examine recent evidence indicating that gut microbiota uphold intrinsic IFN signaling, which extensively involved lipid metabolism. However, prolonged responses obesogenesis comprise reciprocal causality between susceptibility Furthermore, some subtypes therapeutic potency their anti-inflammation anti-obesity activity.

Язык: Английский

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mTOR Overcomes Multiple Metabolic Restrictions to Enable HIV-1 Reverse Transcription and Intracellular Transport

Cell Reports, Год журнала: 2020, Номер 31(12), С. 107810 - 107810

Опубликована: Июнь 1, 2020

Cellular metabolism governs the susceptibility of CD4 T cells to HIV-1 infection. Multiple early post-fusion steps replication are restricted in resting peripheral blood cells; however, molecular mechanisms that underlie metabolic control these remain undefined. Here, we show mTOR activity following cell stimulatory signals overcomes restrictions by enabling expansion dNTPs fuel reverse transcription (RT), as well increasing acetyl-CoA stabilize microtubules transport RT products. We find catalytic inhibition diminishes pools both metabolites limiting glucose and glutamine utilization several pathways, thereby suppressing demonstrate how mTOR-coordinated biosyntheses enable replication, add which inhibitors block HIV-1, identify some modules downstream druggable targets for inhibition.

Язык: Английский

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Pathogens MenTORing Macrophages and Dendritic Cells: Manipulation of mTOR and Cellular Metabolism to Promote Immune Escape

Cells, Год журнала: 2020, Номер 9(1), С. 161 - 161

Опубликована: Янв. 9, 2020

Myeloid cells, including macrophages and dendritic represent an important first line of defense against infections. Upon recognition pathogens, these cells undergo a metabolic reprogramming that supports their activation ability to respond the invading pathogens. An regulator is mammalian target rapamycin (mTOR). During infection, pathogens use host pathways scavenge nutrients, as well for subversion immune response together facilitate pathogen survival. Given pivotal role mTOR in controlling metabolism DC macrophage function, have evolved strategies this pathway manipulate cells. This review seeks discuss most recent insights into how subvert potential deleterious responses them, by focusing on are known regulate be regulated signaling amino acid, lipid carbohydrate metabolism, autophagy.

Язык: Английский

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Metabolomics Profiles Reveal New Insights of Herpes Simplex Virus Type 1 Infection

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(2), С. 1521 - 1521

Опубликована: Янв. 12, 2023

Herpes simplex virus type 1 (HSV-1) is a ubiquitous human pathogen that can cause significant morbidity, primarily facial cold sores and herpes encephalitis. Previous studies have shown variety of viruses reprogram the metabolic profiles host cells to facilitate self-replication. In order further elucidate interactions between cell HSV-1, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyze in lung fibroblasts KMB17 infected with HSV-1. The results showed 654 474 differential metabolites were identified positive negative ion modes, respectively, 169 114 pathways might be altered screened. These are mainly involved central carbon metabolism, choline amino acid purine pyrimidine cholesterol bile secretion, prolactin signaling pathway. Further, confirmed addition tryptophan metabolite kynurenine promotes HSV-1 replication, 25-Hydroxycholesterol inhibits viral replication. Significantly, replication was obviously enhanced ChOKα (a rate-limiting enzyme) deficient mouse macrophages. indicated induces reprogramming promote or resist Taken together, these observations highlighted significance metabolism which would help clarify pathogenesis identify new anti-HSV-1 therapeutic targets.

Язык: Английский

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NAD+-consuming enzymes in immune defense against viral infection

Biochemical Journal, Год журнала: 2021, Номер 478(23), С. 4071 - 4092

Опубликована: Дек. 6, 2021

The COVID-19 pandemic reminds us that in spite of the scientific progress past century, there is a lack general antiviral strategies. In analogy to broad-spectrum antibiotics as antibacterial agents, developing broad spectrum agents would buy time for development vaccines and treatments future viral infections. addition targeting factors, possible strategy understand host immune defense mechanisms develop methods boost response. Here we summarize role NAD+-consuming enzymes against infections, with hope better understanding this process could help therapeutics these enzymes. These include PARPs, sirtuins, CD38, SARM1. Among these, function PARPs particularly important will be focus review. Interestingly, NAD+ biosynthetic are also implicated responses. addition, many viruses, including SARS-CoV-2 contain macrodomain-containing protein (NSP3 SARS-CoV-2), which serves counteract PARPs. Therefore, play crucial roles responses infections detailed mechanistic understandings likely facilitate

Язык: Английский

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Kinetics of transcriptional response against poly (I:C) and infectious salmon anemia virus (ISAV) in Atlantic salmon kidney (ASK) cell line

Developmental & Comparative Immunology, Год журнала: 2020, Номер 110, С. 103716 - 103716

Опубликована: Апрель 28, 2020

Vaccine adjuvants induce host innate immune responses improving long-lasting adaptive immunity against vaccine antigens. In vitro models can be used to compare these between and the infection targeted by vaccine. We utilized transcriptomic profiling of an Atlantic salmon cell line ISAV experimental viral adjuvant: poly (I:C). Induction interferon induced genes were observed after both treatments, but often with different amplitude kinetics. Using KEGG ortholog database available software from Bioconductor we could specify a complete bioinformatic pipeline for analysis data salmon, feature not previously available. have identified important differences in transcriptional profile cells exposed adjuvant candidate, This report increases our knowledge host-pathogen interaction which extent mimicked compounds.

Язык: Английский

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Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis

eLife, Год журнала: 2021, Номер 10

Опубликована: Авг. 23, 2021

Arthropod-borne rickettsial pathogens cause mild and severe human disease worldwide. The tick-borne pathogen Rickettsia parkeri elicits skin lesions (eschars) disseminated in humans; however, inbred mice are generally resistant to infection. We report that intradermal infection of lacking both interferon receptors (Ifnar1-/-;Ifngr1-/-) with as few 10 R. eschar formation disseminated, lethal disease. Similar infection, eschars exhibited necrosis inflammation, bacteria primarily found leukocytes. Using this model, we find the actin-based motility factor Sca2 is required for dissemination from internal organs, outer membrane protein OmpB contributes formation. Immunizing Ifnar1-/-;Ifngr1-/- sca2 ompB mutant protects against rechallenge, revealing live-attenuated vaccine candidates. Thus, a tractable model investigate rickettsiosis, virulence factors, immunity. Our results further suggest discrepancies between mouse susceptibility may be due differences signaling.

Язык: Английский

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Studies in the antiviral molecular mechanisms of 25-hydroxycholesterol: Disturbing cholesterol homeostasis and post-translational modification of proteins

European Journal of Pharmacology, Год журнала: 2022, Номер 926, С. 175033 - 175033

Опубликована: Май 19, 2022

Язык: Английский

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