How Viral and Intracellular Bacterial Pathogens Reprogram the Metabolism of Host Cells to Allow Their Intracellular Replication

Frontiers in Cellular and Infection Microbiology, Год журнала: 2019, Номер 9

Опубликована: Март 4, 2019

Viruses and intracellular bacterial pathogens (IBPs) have in common the need of suitable host cells for efficient replication proliferation during infection. In human infections, cell types which both groups are using as hosts indeed quite similar include phagocytic immune cells, especially monocytes/macrophages dendritic well nonprofessional phagocytes, like epithelial fibroblasts endothelial cells. These terminally differentiated normally a metabolically quiescent state when they encountered by these This metabolic does not meet extensive nutrients required viruses IBPs which, contrast to viral pathogens, perform their own specific metabolism survive efficiently replicate niches. For this goal, reprogram pathogen-specific manner increase supply nutrients, energy metabolites be provided pathogen allow its replication. appears often achieved interaction factors with central regulators, including oncogenes tumor suppressors, or introduction virus-specific oncogenes. Less is so far known on mechanisms leading reprogramming IBPs. However, still scant data suggest that may also determine IBP infections. review, we summarize compare present knowledge important, yet poorly understood aspect pathogenesis

Язык: Английский

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Glycolysis Is an Intrinsic Factor for Optimal Replication of a Norovirus

mBio, Год журнала: 2019, Номер 10(2)

Опубликована: Март 11, 2019

Viruses depend on the host cells they infect to provide machinery and substrates for replication. Host are highly dynamic systems that can alter their intracellular environment metabolic behavior, which may be helpful or inhibitory an infecting virus. In this study, we show macrophages, a target cell of murine norovirus (MNV), increase glycolysis upon viral infection, is important early steps in MNV infection. Human noroviruses (hNoV) major cause gastroenteritis globally, causing enormous morbidity economic burden. Currently, no effective antivirals vaccines exist hNoV, mainly due lack high-efficiency vitro culture models study. Thus, insights gained from model reveal aspects metabolism targeted improving hNoV developing antiviral therapies.

Язык: Английский

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The roles of lipids in SARS-CoV-2 viral replication and the host immune response

Journal of Lipid Research, Год журнала: 2021, Номер 62, С. 100129 - 100129

Опубликована: Янв. 1, 2021

The significant morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 infection has underscored the need for novel antiviral strategies. Lipids play essential roles in viral life cycle. lipid composition of cell membranes can influence entry by mediating fusion or affecting receptor conformation. Upon infection, viruses reprogram cellular metabolism to remodel fuel production new virions. Furthermore, several classes mediators, including eicosanoids sphingolipids, regulate host immune response infection. Here, we summarize existing literature on mechanisms through which these mediators may burden COVID-19. define gaps knowledge identify core areas lipids offer therapeutic promise 2.

Язык: Английский

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Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Окт. 16, 2020

Abstract Macrophages play an essential role in the early immune response against Toxoplasma and are cell type preferentially infected by parasite vivo. Interferon gamma (IFNγ) elicits a variety of anti- activities macrophages. Using genome-wide CRISPR screen we identify 353 genes that determine fitness naїve or IFNγ-activated murine macrophages, seven which further confirmed. We show one these encodes dense granule protein GRA45, has chaperone-like domain, is critical for correct localization GRAs into PVM secretion GRA effectors host cytoplasm. Parasites lacking GRA45 more susceptible to IFNγ-mediated growth inhibition have reduced virulence mice. Together, characterize important provide resource community explore function

Язык: Английский

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Host metabolic reprogramming in response to SARS-CoV-2 infection: A systems biology approach

Microbial Pathogenesis, Год журнала: 2021, Номер 158, С. 105114 - 105114

Опубликована: Июль 30, 2021

Язык: Английский

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Metabolism and Innate Immunity Meet at the Mitochondria

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Июль 27, 2021

Mitochondria are master regulators of metabolism and have emerged as key signalling organelles the innate immune system. Each mitochondrion harbours potent agonists inflammation, including mitochondrial DNA (mtDNA), which normally shielded from rest cell extracellular environment therefore do not elicit detrimental inflammatory cascades. Mitochondrial damage dysfunction can lead to cytosolic exposure mtDNA, triggers inflammation in a number diseases autoimmune neurodegenerative disorders. However, recent research has revealed that extra-mitochondrial mtDNA is solely negative consequence pointed an active role mitochondria immunity. Metabolic cues nucleotide imbalance stimulate release order drive type I interferon response. Moreover, important effectors response pathogen infection, such antiviral protein (MAVS), located at surface modulated by cellular metabolic status dynamics. In this review, we explore how why immunity converge describe orchestrate pathways different scenarios. Understanding programming translated into responses bears relevance broad range human cancer.

Язык: Английский

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TB and COVID-19: An Exploration of the Characteristics and Resulting Complications of Co-infection

Frontiers in Bioscience-Scholar, Год журнала: 2022, Номер 14(1)

Опубликована: Март 1, 2022

Tuberculosis (TB) and Coronavirus Disease-19 (COVID-19) infection are two respiratory diseases that of particular concern epidemiologically. is one the oldest recorded in history mankind dating back thousands years. It estimated approximately quarter world's population infected with latent Mycobacterium tuberculosis (LTBI). This contrasts COVID-19, which emerged late 2019. Data continues to accumulate become available on this pathogen, but long-term side effect fibrotic damage COVID-19 patients evokes parallels between novel coronavirus its ancient bacterial affiliate. similarity as well several others may incite inquiries whether coinfection individuals TB severe acute syndrome 2 (SARS-CoV-2) lead excessive fibrosis lungs thus emergence an active infection. While it understood how leads structural immunological lung complications including granuloma formation, fibrosis, T cell exhaustion, less known about disease course when SARS-CoV-2 present. Past present research demonstrate IL-10, TNF-α, IFN class I-III, TGF-β, IL-35, Regulatory cells (T-regs) all important contributors characteristics host response mycobacterium tuberculosis. has also been noted current I, II, III, ACE-2, T-regs virus different ways than they pathogen. Both pathogens unbalanced inflammatory immune response, together a shared dysregulation suggests increased risk severity progression both diseases. We have reviewed 72 manuscripts years 1992 2021. The pertaining SARS-COV-2 specifically from 2020 Our literature review aims explore biomolecular effects these pathogenicity along publications TB/COVID-19 coinfection, focusing TB, challenges treating during pandemic. compiled material will then aid latticework foundation knowledge for future leading hopeful improved system therapeutic strategies coinfection.

Язык: Английский

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Diverse Functions of Polyamines in Virus Infection

Biomolecules, Год журнала: 2020, Номер 10(4), С. 628 - 628

Опубликована: Апрель 18, 2020

As obligate intracellular parasites, viruses rely on host cells for the building blocks of progeny viruses. Metabolites such as amino acids, nucleotides, and lipids are central to viral proteins, genomes, envelopes, availability these molecules can restrict or promote infection. Polyamines, comprised putrescine, spermidine, spermine in mammalian cells, also critical virus Polyamines small, positively charged that function transcription, translation, cell cycling. Initial work polyamines bacteriophage infection illuminated In decades since early virus-polyamine descriptions, diverse continues highlight a role processes, including genome packaging enzymatic activity. On side, response Thus, hosts compete polyamines, which resource both. Pharmacologically targeting tipping balance favor replication, holds significant promise broad-spectrum antiviral strategy.

Язык: Английский

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25-Hydroxycholesterol in health and diseases

Journal of Lipid Research, Год журнала: 2023, Номер 65(1), С. 100486 - 100486

Опубликована: Дек. 16, 2023

Язык: Английский

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Glutaminolysis of CD4+ T Cells: A Potential Therapeutic Target in Viral Diseases

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 603 - 616

Опубликована: Фев. 1, 2024

Abstract: CD4 + T cells play a critical role in the pathogenesis of viral diseases, which are activated by internal metabolic pathways encountering with antigens. Glutaminolysis converts glutamine into tricarboxylic acid (TCA) circulating metabolites α-ketoglutaric acid, is essential for proliferation and differentiation plays central providing energy structural components needed replication after virus hijacks host cell. Changes glutaminolysis accompanied changes status cell due to competition between immune cells. More recently, attempts have been made treat tumours, autoimmune diseases altering breakdown In this review, we will discuss current knowledge subsets from not only increasing our understanding immunometabolism but also new perspective therapeutic target diseases. Keywords: cells, glutamine, glutaminolysis, response

Язык: Английский

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