Role of mouse adenovirus type 1 E4orf6-induced degradation of protein kinase R in pathogenesis DOI Creative Commons

David F. Edwards,

Estela A. Pereira, Luíza Antunes de Castro-Jorge

и другие.

Journal of Virology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 31, 2024

Protein kinase R (PKR) is an interferon-induced antiviral protein activated by autophosphorylation in response to double strand DNA (dsRNA) and other stimuli. Activated PKR causes translation inhibition apoptosis, it contributes proinflammatory responses, cell growth, differentiation. Mouse adenovirus type 1 (MAV-1) counteracts causing its degradation via a viral protein, early region 4 open reading frame 6 (E4orf6). Degradation dependent on E4orf6 binding Cullin 2, component of the MAV-1 ubiquitin ligase. We investigated importance for induction exploiting ability infect natural host with MAV-1. First, we used new PKR-deficient mouse strain, PKR-TKO. PKR-TKO embryo fibroblasts (MEFs) produced higher levels upon infection than did wild-type (WT) MEFs. mice had significantly reduced survival, lower LD

Язык: Английский

Phase separation as a new form of regulation in innate immunity DOI
Lei Wang, Wen Zhou

Molecular Cell, Год журнала: 2024, Номер 84(13), С. 2410 - 2422

Опубликована: Июнь 26, 2024

Язык: Английский

Процитировано

11
A Wonderful Journey: The Diverse Roles of Adenosine Deaminase Action on RNA 1 (ADAR1) in Central Nervous System Diseases DOI Creative Commons
Lin Cheng, Ziying Liu,

Chunxiao Shen

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(1)

Опубликована: Янв. 1, 2025

ABSTRACT Background Adenosine deaminase action on RNA 1 (ADAR1) can convert the adenosine in double‐stranded (dsRNA) molecules into inosine a process known as A‐to‐I editing. ADAR1 regulates gene expression output by interacting with and other proteins; plays important roles development, including growth; is linked to innate immunity, tumors, central nervous system (CNS) diseases. Results In recent years, role of tumors has been widely discussed, but its CNS diseases not reviewed. It worth noting that studies have shown great potential treatment neurodegenerative diseases, mechanisms are still unclear. Therefore, it necessary elaborate Conclusions Here, we focus effects such Aicardi–AicardiGoutières syndrome, Alzheimer's disease, Parkinson's glioblastoma, epilepsy, amyotrophic lateral sclerosis, autism. We also evaluate impact ADAR1‐based strategies these particular development new technologies microRNAs, nanotechnology, editing, stem cell therapy. hope provide directions insights for future editing technology brain science

Язык: Английский

Процитировано

1
Bacteriophage derived dsRNA induces polarized activation of alveolar macrophages from Balb/c and C57Bl/6 mice in vitro in sex- and age-dependent manner DOI
R. Dovhyi,

A. Dvukhriadkina,

K. Ostrovska

и другие.

Cellular Immunology, Год журнала: 2025, Номер 408, С. 104916 - 104916

Опубликована: Янв. 4, 2025

Язык: Английский

Процитировано

1
A Novel Self‐Amplifying mRNA with Decreased Cytotoxicity and Enhanced Protein Expression by Macrodomain Mutations DOI Creative Commons
Yue Gong,

Danni Yong,

Gensheng Liu

и другие.

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Сен. 23, 2024

Abstract The efficacy and safety of self‐amplifying mRNA (saRNA) have been demonstrated in COVID‐19 vaccine applications. Unlike conventional non‐replicating (nrmRNA), saRNA offers a key advantage: its self‐replication mechanism fosters efficient expression the encoded protein, leading to substantial dose savings during administration. Consequently, there is growing interest further optimizing efficiency saRNA. In this study, vitro adaptive passaging conducted under exogenous interferon pressure, which revealed several mutations nonstructural protein (NSP). Notably, two stable mutations, Q48P I113F, situated NSP3 macrodomain (MD), attenuated mono adenosine diphosphate ribose (MAR) hydrolysis activity exhibited decreased replication but increased payload compared wild‐type (wt saRNA). Transcriptome sequencing analysis unveils diminished activation double‐stranded RNA (dsRNA) sensor and, consequently, significantly reduced innate immune response wt Furthermore, mutant less translation inhibition cell apoptosis than saRNA, culminating higher both vivo. These findings underscore potential reducing replication‐dependent dsRNA‐induced responses through genetic modification as valuable strategy for enhancing efficiency, mitigating cytotoxicity.

Язык: Английский

Процитировано

7
Interferonopathies: From concept to clinical practice DOI Creative Commons
Leonardo Oliveira Mendonça, Marie‐Louise Frémond

Best Practice & Research Clinical Rheumatology, Год журнала: 2024, Номер unknown, С. 101975 - 101975

Опубликована: Авг. 1, 2024

The horror autoinflammaticus derived from aberrant type I interferon secretion determines a special group of autoinflammatory diseases named interferonopathies. Diverse mechanisms involved in nucleic acids sensing, metabolizing or the lack signaling retro-control are responsible for phenotypes associated to Aicardi-Goutières Syndrome (AGS), Proteasome-Associated Autoinflammatory Diseases (PRAAS), STING-Associated Vasculopathy with Infancy Onset (SAVI) and certain forms monogenic Systemic lupus erythematosus (SLE). This review approaches interferonopathies basic immunogenetic concept diagnosis treatment.

Язык: Английский

Процитировано

4
PANoptosis in autoimmune diseases interplay between apoptosis, necrosis, and pyroptosis DOI Creative Commons

Kangnan Liu,

Mi Wang,

Dongdong Li

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Окт. 31, 2024

PANoptosis is a newly identified inflammatory programmed cell death (PCD) that involves the interplay of apoptosis, necrosis, and pyroptosis. However, its overall biological effects cannot be attributed to any one type PCD alone. regulated by signaling cascade triggered recognition pathogen-associated molecular patterns (PAMPs) damage-associated (DAMPs) various sensors. This triggers assembly PANoptosome, which integrates key components from other pathways via adapters ultimately activates downstream execution molecules, resulting in with necrotic, apoptotic, pyroptotic features. Autoimmune diseases are characterized reduced immune tolerance self-antigens, leading abnormal responses, often accompanied systemic chronic inflammation. Consequently, PANoptosis, as unique innate immune-inflammatory pathway, has significant pathophysiological relevance inflammation autoimmunity. most previous research on focused tumors infectious diseases, leaving activation role autoimmune unclear. review briefly outlines characteristics summarizes several PANoptosome complexes, their mechanisms, components. We also explored dual potential therapeutic approaches targeting PANoptosis. Additionally, we existing evidence for explore regulatory mechanisms involved.

Язык: Английский

Процитировано

4
Eastern equine encephalitis virus: Pathogenesis, immune response, and clinical manifestations DOI Creative Commons
Bhupesh Parashar, Rishabha Malviya, Sathvik Belagodu Sridhar

и другие.

Infectious Medicine, Год журнала: 2025, Номер 4(1), С. 100167 - 100167

Опубликована: Янв. 18, 2025

Язык: Английский

Процитировано

0
Innate Sensing of Viral Nucleic Acids and Their Use in Antiviral Vaccine Development DOI Creative Commons
Takuji Enya, Susan R. Ross

Vaccines, Год журнала: 2025, Номер 13(2), С. 193 - 193

Опубликована: Фев. 16, 2025

Viruses pose a significant threat to humans by causing numerous infectious and potentially fatal diseases. Understanding how the host's innate immune system recognizes viruses is essential understanding pathogenesis ways control viral infection. Innate immunity also plays critical role in shaping adaptive responses induced vaccines. Recently developed adjuvants often include nucleic acids that stimulate pattern recognition receptors which are components of necessary for activating antigen-presentation cells thereby bridging immunity. Therefore, acid sensing cytosolic sensors essential, as it provides potential means developing new vaccine strategies, including effective adjuvants.

Язык: Английский

Процитировано

0
Modulation of the Toll-like Receptor 3-Mediated Intestinal Immune Response by Water Kefir DOI Creative Commons
Stefanía Dentice Maidana, Ramiro Ortiz Moyano,

Mariano Elean

и другие.

Microbiology Research, Год журнала: 2024, Номер 15(3), С. 1239 - 1250

Опубликована: Июль 20, 2024

Kefir has been associated with beneficial effects on its host’s health. The previous works examining the impact of kefir immune system focused milk or exopolysaccharides and bacterial strains derived from it, while water not evaluated. Furthermore, studies have kefir’s ability to modulate hemostasis exert anti-inflammatory effects, specific action antiviral immunity investigated. Thus, aim this work was examine potential immunomodulatory intestinal innate mediated by Toll-like receptor-3 (TLR3). Adult BALB/c mice fed ad libitum, diluted 1:5, 1:10, 1:20 in drinking water, for 6 consecutive days. On day 7, treated groups untreated control received an intraperitoneal injection TLR3 agonist poly(I:C). Two days after activation, damage response were studied. administration poly(I:C) induced inflammatory-mediated tissue damage, characterized upregulation interferons (IFNs), pro-inflammatory mediators (TNF-α, IL-15, IL-6), factors involved epithelial destruction (RAE-1 NKG2D). histological analysis small samples showed that receiving 1:5 exhibited reduced edema a lower inflammatory cell infiltration. Kefir-treated had significantly levels serum LDH, AST, ALT as well TNF-α, IL-6, RAE-1, NKG2D. This group also higher concentrations IFN-β, IFN-γ, IL-10. treatment 1:10 modulated cytokines but effect than treatment, did modify parameters evaluated compared mice. results indicate exerts dose-dependent manner. vivo allow us speculate can induce two TLR3-mediated response: enhancement defenses protection against damage. These protective require further exploration understand how kefir, molecules/strains, influence determine extent real viral challenge.

Язык: Английский

Процитировано

2
Molecular Circuits of Immune Sensing and Response to Oncolytic Virotherapy DOI Open Access
Darshak Bhatt, Toos Daemen

Опубликована: Март 26, 2024

Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment, utilizing viruses to preferentially infect and eliminate cells while stimulating immune responses. In this review we synthesize current literature on the molecular circuits of sensing response oncolytic virotherapy; focusing viral DNA or RNA by infected cells, cytokine danger-associated signal neighboring subsequent downstream activation pathways. The sequential sense-and-response mechanisms involve triggering sensors activate transcription factors related genes breadth We describe how signals induced in tumor upon can trigger diverse signaling pathways, activating both antigen-presenting cell-based innate T adaptive Insights into these complex provide valuable knowledge enhancing strategies.

Язык: Английский

Процитировано

1