IFITM3 inhibits severe fever with thrombocytopenia syndrome virus entry and interacts with viral Gc protein

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(3)

Published: Feb. 25, 2024

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic disease high fatality rate of 10%-20%. Vaccines or specific therapeutic measures remain lacking. Human interferon inducible transmembrane protein 3 (hIFITM3) a broad-spectrum antiviral factor targeting viral entry. However, the activity hIFITM3 against SFTS virus (SFTSV) and functional mechanism IFITM3 remains unclear. Here we demonstrate that endogenous provides protection SFTSV infection participates in anti-SFTSV effect type Ⅰ Ⅲ interferons (IFNs). overexpression exhibits function by blocking Gn/Gc-mediated entry fusion. Further studies showed binds Gc directly its intramembrane domain (IMD) responsible for this interaction restriction Mutation two neighboring cysteines on IMD weakens IFITM3-Gc attenuates IFITM3, suggesting may partly mediate inhibition Overall, our data first time plays critical role IFNs-mediated response, uncover novel infection, highlighting potential clinical intervention disease.

Language: Английский

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Single-Cell Analysis Reveals Heterogeneity of Virus Infection, Pathogenicity, and Host Responses: HIV as a Pioneering Example

Annual Review of Virology, Journal Year: 2020, Volume and Issue: 7(1), P. 333 - 350

Published: Sept. 29, 2020

While analyses of cell populations provide averaged information about viral infections, single-cell offer individual consideration, thereby revealing a broad spectrum diversity as well identifying extreme phenotypes that can be exploited to further understand the complex virus-host interplay. Single-cell technologies applied in context human immunodeficiency virus (HIV) infection proved valuable tools help uncover specific biomarkers novel candidate players interactions. This review aims at providing an updated overview field HIV and acquired knowledge on infection, latency, host response. Although is pioneering example, similar approaches have proven for elucidating behavior interplay range other viruses.

Language: Английский

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Emerging Role of PYHIN Proteins as Antiviral Restriction Factors

Viruses, Journal Year: 2020, Volume and Issue: 12(12), P. 1464 - 1464

Published: Dec. 18, 2020

Innate immune sensors and restriction factors are cellular proteins that synergize to build an effective first line of defense against viral infections. usually constitutively expressed capable detecting pathogen-associated molecular patterns (PAMPs) via specific pattern recognition receptors (PRRs) stimulate the response. Restriction frequently upregulated by interferons (IFNs) may inhibit pathogens at essentially any stage their replication cycle. Members Pyrin hematopoietic interferon-inducible nuclear (HIN) domain (PYHIN) family have initially been recognized as important foreign nucleic acids activators inflammasome IFN Accumulating evidence shows, however, least three four members human PYHIN restrict independently sensing innate activation. In this review, we provide overview on role in antiviral countermeasures.

Language: Английский

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Glutamylation of an HIV-1 protein inhibits the immune response by hijacking STING

Cell Reports, Journal Year: 2023, Volume and Issue: 42(5), P. 112442 - 112442

Published: April 25, 2023

Cyclic GMP-AMP synthase (cGAS) recognizes Y-form cDNA of human immunodeficiency virus type 1 (HIV-1) and initiates antiviral immune response through cGAS-stimulator interferon genes (STING)-TBK1-IRF3-type I (IFN-I) signalingcascade. Here, we report that the HIV-1 p6 protein suppresses HIV-1-stimulated expression IFN-I promotes evasion. Mechanistically, glutamylated at residue Glu6 inhibits interaction between STING tripartite motif 32 (TRIM32) or autocrine motility factor receptor (AMFR). This subsequently K27- K63-linked polyubiquitination K337, therefore inhibiting activation, whereas mutation partially reverses inhibitory effect. However, CoCl2, an agonist cytosolic carboxypeptidases (CCPs), counteracts glutamylation These findings reveal a mechanism which mediates evasion provides therapeutic drug candidate to treat infection.

Language: Английский

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Daxx Inhibits HIV-1 Reverse Transcription and Uncoating in a SUMO-Dependent Manner

Viruses, Journal Year: 2020, Volume and Issue: 12(6), P. 636 - 636

Published: June 11, 2020

Death domain-associated protein 6 (Daxx) is a multifunctional, ubiquitously expressed and highly conserved chaperone involved in numerous cellular processes, including apoptosis, transcriptional repression, carcinogenesis. In 2015, we identified Daxx as an antiretroviral factor that interfered with HIV-1 replication by inhibiting the reverse transcription step. present study, sought to unravel molecular mechanism of Daxx-mediated restriction and, particular, identify protein(s) targets order achieve its antiviral activity. First, show SUMO-interacting motif (SIM) located at C-terminus strictly required for inhibit transcription. By performing quantitative proteomic screen combined classical biochemical analyses, found associated incoming cores through SIM-dependent interaction cyclophilin A (CypA) capsid (CA). was reside within multiprotein complex viral capsids, also containing TNPO3, TRIM5α, TRIM34. Given well-known influence these factors on stability cores, investigated effect cytoplasmic fate prevented uncoating manner. Altogether, our findings suggest that, recruiting TRIM34 possibly other proteins onto CA-bound CypA, increases their stability, thus preventing Our study uncovers previously unknown function early steps infection further illustrates how are two tightly interdependent processes.

Language: Английский

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Evolution of a concept: From accessory protein to key virulence factor, the case of HIV-1 Vpr

Biochemical Pharmacology, Journal Year: 2020, Volume and Issue: 180, P. 114128 - 114128

Published: June 30, 2020

Language: Английский

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IBD Subtype-Regulators IFNG and GBP5 Identified by Causal Inference Drive More Intense Innate Immunity and Inflammatory Responses in CD Than Those in UC

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: April 6, 2022

Background: The pathological differences between Crohn’s disease (CD) and ulcerative colitis (UC) are substantial unexplained yet. Here, we aimed to identify potential regulators that drive different pathogenesis of CD UC by causal inference analysis transcriptome data. Methods: Kruskal–Wallis Dunnett’s tests were performed differentially expressed genes (DEGs) among patients, controls. Subsequently, pathways (DEPs) identified used construct the interaction network DEPs. Causal was IBD subtype-regulators. expression subtype-regulators their downstream validated qRT-PCR with an independent cohort. Results: Compared control group, 1,352 2,081 DEGs in groups, respectively. Multiple DEPs closely related inflammation-related pathways, such as NOD-like receptor signaling, IL-17 chemokine signaling pathways. Based on priori DEPs, IFNG GBP5 results discovery cohort showed level , NLRP3 significantly higher group than group. regulation relationships confirmed data from qRT-PCR. Conclusion: Our study suggests trigger more intense innate immunity inflammatory responses those UC. findings reveal pathomechanical may contribute personalized treatment for

Language: Английский

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IDO1, FAT10, IFI6, and GILT Are Involved in the Antiretroviral Activity of γ-Interferon and IDO1 Restricts Retrovirus Infection by Autophagy Enhancement

Cells, Journal Year: 2022, Volume and Issue: 11(14), P. 2240 - 2240

Published: July 19, 2022

Gamma-interferon (γ-IFN) significantly inhibits infection by replication-defective viral vectors derived from the human immunodeficiency virus type 1 (HIV-1) or murine leukemia (MLV) but underlying mechanism remains unclear. Previously we reported that knockdown of γ-IFN-inducible lysosomal thiolreductase (GILT) abrogates antiviral activity γ-IFN in TE671 cells not HeLa cells, suggesting other host factors are involved its cells. We identified cellular factors, expression which induced using a microarray, and analyzed effects 11 γ-IFN-induced on retroviral vector infection. Our results showed exogenous FAT10, IFI6, IDO1 both HIV-1- MLV-based infections. The was decreased function IDO1, GILT were simultaneously inhibited. is an enzyme metabolizes essential amino acid, tryptophan. However, did restrict Atg3-silencing autophagy occur. This study found γ-IFN, inducing autophagy.

Language: Английский

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Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection

Frontiers in Cellular and Infection Microbiology, Journal Year: 2021, Volume and Issue: 11

Published: Sept. 21, 2021

The induction of antiviral effector proteins as part a homeostatically controlled innate immune response to infection plays critical role in limiting the propagation and transmission respiratory pathogens. However, prolonged this can lead lung hyperinflammation, tissue damage, failure. We hypothesized that tissues exposed constant threat may constitutively express higher levels reduce need activate potentially harmful defences. By analysing transcriptomic data derived from range human tissues, we identify genes relative other mucosal non-mucosal tissues. using primary cell lines airways rhesus macaques, show interferon-stimulated protein TRIM22 (TRIpartite Motif 22) be expressed independently viral or stimulation. These findings contrast with previous reports have shown expression laboratory-adapted require interferon demonstrate constitutive are sufficient inhibit onset avian influenza A virus (IAV) by restricting transcription interferon-mediated Thus, confer pre-existing (intrinsic) intracellular defence against IAV cells tract. Our highlight importance tissue-specific cell-type dependent patterns gene restriction outset infection.

Language: Английский

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MiR-155 Negatively Regulates Anti-Viral Innate Responses among HIV-Infected Progressors

Viruses, Journal Year: 2023, Volume and Issue: 15(11), P. 2206 - 2206

Published: Nov. 1, 2023

HIV infection impairs host immunity, leading to progressive disease. An anti-retroviral treatment efficiently controls viremia but cannot completely restore the immune dysfunction in HIV-infected individuals. Both and viral factors determine rate of disease progression. Among factors, innate immunity plays a critical role; however, mechanism(s) associated with dysfunctional responses are poorly understood among progressors, which was investigated here. The gene expression profiles TLRs cytokines (LTNPs progressors) HIV-uninfected individuals were examined. Since progressors showed dysregulated TLR-mediated response, we role TLR agonists restoring functions progressors. stimulation PBMCs TLR3 agonist-poly:(I:C), TLR7 agonist-GS-9620 TLR9 agonist-ODN 2216 resulted an increased IFN-α, IFN-β IL-6. Interestingly, IFITM3, BST-2, IFITM-3, IFI-16 also upon agonists, respectively. To further understand molecular mechanism involved, miR-155 explored. Increased noted MiR-155 inhibition upregulated TLR3, NF-κB, IRF-3, TNF-α APOBEC-3G, BST-2 genes conclude, negatively regulates as wel l restriction play important mounting anti-HIV responses; hence, targeting might be helpful devising strategic approaches towards alleviating

Language: Английский

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