The Unusual Role of Ribonuclease L in Innate Immunity DOI Creative Commons

Agnes Karasik,

Nicholas R. Guydosh

Wiley Interdisciplinary Reviews - RNA, Год журнала: 2024, Номер 15(6)

Опубликована: Ноя. 1, 2024

ABSTRACT Ribonuclease L is an endonuclease that activated as part of the dsRNA‐driven innate immune response. Active RNase cleaves pathogenic RNAs a way to eliminate infections. However, there are additional and unexpected ways causes changes in host promote response contribute its role defense. Central these unconventional mechanisms observation also degrades mRNA host. In turn, fragments generates can be translated. This activation ribosome collision sensor leads downstream signaling cell death. Additionally, liberation RNA binding proteins after decay appears affect gene expression. this review, we discuss other recent advances focus on novel unusual contributes immunity.

Язык: Английский

The canonical antiviral protein oligoadenylate synthetase 1 elicits antibacterial functions by enhancing IRF1 translation DOI
Munesh Kumar Harioudh,

Joseph Pérez,

Lomon So

и другие.

Immunity, Год журнала: 2024, Номер 57(8), С. 1812 - 1827.e7

Опубликована: Июль 1, 2024

Язык: Английский

Процитировано

5

Interferon-stimulated genes and their antiviral activity against SARS-CoV-2 DOI Creative Commons
Ana María Ortega-Prieto, Jose M. Jiménez-Guardeño

mBio, Год журнала: 2024, Номер 15(9)

Опубликована: Авг. 22, 2024

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic remains an international health problem caused by the recent emergence of severe acute respiratory syndrome 2 (SARS-CoV-2). As May 2024, SARS-CoV-2 has more than 775 million cases and over 7 deaths globally. Despite current vaccination programs, infections are still rapidly increasing, mainly due to appearance spread new variants, variations in immunization rates, limitations vaccines preventing transmission. This underscores need for pan-variant antivirals treatments. interferon (IFN) system is a critical element innate immune response serves as frontline defense against viruses. It induces generalized antiviral state transiently upregulating hundreds IFN-stimulated genes (ISGs). To gain deeper comprehension SARS-CoV-2, its connection COVID-19 pathogenesis, potential therapeutic implications, this review provides detailed overview fundamental aspects diverse ISGs identified their properties SARS-CoV-2. emphasizes importance these proteins controlling viral replication spread. Furthermore, we explore methodological approaches identification conduct comparative analysis with other Deciphering roles interactions pathogens can help identify novel targets therapies enhance our preparedness confront future threats.

Язык: Английский

Процитировано

3

West Nile Virus (WNV): One-Health and Eco-Health Global Risks DOI Creative Commons
Luigi Bruno,

Maria Anna Nappo,

Raffaele Frontoso

и другие.

Veterinary Sciences, Год журнала: 2025, Номер 12(3), С. 288 - 288

Опубликована: Март 19, 2025

West Nile virus (WNV) is an important zoonotic pathogen belonging to the Flaviviridae family, which endemic in some areas and emerging others. WNV transmitted by blood-sucking mosquitoes of genus Culicoides, Aedes, Anopheles, infection can cause different clinical symptoms. The most common benign illness humans fever (WNF), but a lethal neurological disease (WNND), related neuro-invasiveness lineage 2, represents highest health risk infection. neuro-clinical form recognized mammals (land cetaceans), particularly (elderly or immunosuppressed) horses, avian species, wildlife animals ranging free zoological setting. This review highlights relevant data regarding epidemiology, virology, pathogenesis immunity, signs differential diagnosis, pathology imaging, histopathology gross pathology, economic impact, influence climate change, surveillance WNV. Climate change has favored wide spread many globe consequent One-Health Eco-Health emergencies, influencing human beings, animals, ecosystems.

Язык: Английский

Процитировано

0

Sustained Antigen Stimulation to Evoke and Study Negative feedback Systems responsible for Self-Tolerance/Tumor Immune Escape and transition to the M2 macrophage DOI Creative Commons

Elizabeth Mazzio,

Andrew C. Barnes,

Ramesh Badisa

и другие.

Опубликована: Апрель 18, 2025

Abstract Chronic inflammation plays an obscure role in cancer initiation, with broad references implicating immune exhaustion (IEX) or free radical mediated cell damage. is, however, paradoxically synonymous the term “immune tolerance” which other cases presents itself as a therapeutic limitation to efficacy of tumor therapies particularly those involving microbial -associated molecular patterns (MAMPs) regimens. As “tolerance” remains this day “phenomenon” there is pressing need fully understand every biological aspect apparent negative feedback response, because doing so will serve guide development targeted therapies. In work, we employ rudimentary model, can be adopted it possible provoke through sustained antigen stimulation immunocompetent cells, monitor, define and characterize phenotype evolution using next generation whole transcriptome sequencing + validation studies. This model used study /create vitro “M2” phenotype, involved aggressive tumors synergistic rapid expansion myeloid-derived suppressor cells (MDSCs), dysfunctional CD8+ T cytotoxic (CTL)/ natural killer (NK) cells. Briefly, data shows dominates at 7 11 days, after acute being associated phase specific (time dependent) elevated checkpoints; e.g. PDL1+/MSN, HAVCR2/TIM-3+, SPP1+, C3ar1+, CD73+, IL1RN+, LILRbs+, glycoproteins, integrins etc. Here report on bidirectional changes aligning escape, much centered around loss host defense against viral infection malignancy. Negative rampant induction degradative proteases, SOCS/JAK/STAT/IL-10, CCL2/7 axis tantamount MHC1/2 recognition systems, Type I interferon NOD signaling, antiviral/antibacterial defense, p62/SQSTM also disturbed metabolic signature. The work demonstrates that colloquial terms “tolerance IEX” are somewhat flawed terminology, potent, intentional formidable offense eradicate active arm defense. Truncated /Removed due word count show aligns six distinct chronological differential gene (DEG) expression circumscribe extensive suppression dominate during chronic inflammation. These involve following time dependent patterns: 1) transcripts overexpressed, checkpoint receptors; etc.; 2) overexpressed only chronic; e.g cytokine signaling (SOC3/Jak/Stat), cyto/chemokines (IL-10, CCL2, CCL7), proteases (cathepsins L, D, K, Adam 8, PIM2), adhesives (TSPAN3, QSOX1, PDPN, ITGA5), (PLK2, ADGRE1, CALM1, PCNA, etc.); 3) downregulated severe collective MHC1/II presentation capacity (CD74, H2-Q4, H2-Q6, etc.), (IFN) type systems; 4) only, including OXPHOS/metabolic genes (Aldo A, C, Eno2, Gpi1, (Lyz1, Lyz2, Card19, Ninj1), autophagy-related (p62/SQSTM1). category Tolerance were: 5) induced sharply acute, no longer responsive IFN 1 antiviral response (OAS, BST2, ISG15, ISG20, IRF7, RSAD2/Viperin), TLR2, antibacterial (SAA3, SP140), proinflammatory cytokines (CCL5, TNF, IL1a, IL1b) along IL-1/TLR axis. Last, 6) reverse tolerance, corresponded restored baseline levels maintain mitotic thymosin homeostasis. conclusion, these suggest precipitates feedback, same targets sought today

Язык: Английский

Процитировано

0

Structural basis for OAS2 regulation and its antiviral function DOI Creative Commons
Veronika Merold, Indra Bekere, Stefanie Kretschmer

и другие.

Molecular Cell, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Oligoadenylate synthetase (OAS) proteins are immune sensors for double-stranded RNA and critical restricting viruses. OAS2 comprises two OAS domains, only one of which can synthesize 2'-5'-oligoadenylates RNase L activation. Existing structures OAS1 provide a model enzyme activation, but they do not explain how multiple domains discriminate length. Here, we discover that human exists in an auto-inhibited state as zinc-mediated dimer present mechanism length discrimination: the catalytically deficient domain acts molecular ruler prevents autoreactivity to short RNAs. We demonstrate dimerization myristoylation localize Golgi membranes this is required activation restriction viruses exploit endomembrane system replication, e.g., coronaviruses. Finally, our results highlight non-redundant role emphasize clinical relevance by identifying patient with loss-of-function mutation associated autoimmune disease.

Язык: Английский

Процитировано

0

Epigenetics of atopic dermatitis: pathogenesis and therapeutic prospects DOI
Chao Fang,

Pian Yu,

Jie Li

и другие.

Current Opinion in Immunology, Год журнала: 2025, Номер 95, С. 102581 - 102581

Опубликована: Май 31, 2025

Язык: Английский

Процитировано

0

Finding a foothold to fight: New insights into the viral RNA sensing and activation mechanism of OAS2 DOI
Saumendra N. Sarkar

Molecular Cell, Год журнала: 2025, Номер 85(11), С. 2063 - 2064

Опубликована: Июнь 1, 2025

Язык: Английский

Процитировано

0

Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine DOI Creative Commons
Ivan V. Kuzmin,

Ruben Soto Acosta,

Layne Pruitt

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 30, 2024

Abstract The rodent-borne Andes virus (ANDV) causes a severe disease in humans. We developed an ANDV mRNA vaccine based on the M segment of viral genome, either with regular uridine (U-mRNA) or N1-methylpseudouridine (m1Ψ-mRNA). Female mice immunized by m1Ψ-mRNA slightly greater germinal center (GC) responses than U-mRNA-immunized mice. Single cell RNA and BCR sequencing GC B cells revealed similar levels activation, except additional cluster exhibiting interferon response animals vaccinated U-mRNA but not m1Ψ-mRNA. Similar immunoglobulin class-switching somatic hypermutations were observed to vaccines. Syrian hamsters via prime–boost regimen two doses each vaccine. titers glycoprotein-binding antibodies for construct construct; however, ANDV-neutralizing similar. Vaccinated challenged lethal dose ANDV, along naïve control group. All lower succumbed infection whereas other survived without evidence replication. data demonstrate development protective against lack substantial effect m1Ψ modification immunogenicity protection rodents.

Язык: Английский

Процитировано

2

RECENT INSIGHTS ON PATTERN RECOGNITION RECEPTORS AND THE INTERPLAY OF INNATE IMMUNE RESPONSES AGAINST WEST NILE VIRUS INFECTION DOI

Jatin Behari,

Kajal Yadav, Prashant Khare

и другие.

Virology, Год журнала: 2024, Номер 600, С. 110267 - 110267

Опубликована: Окт. 18, 2024

Язык: Английский

Процитировано

1

A non-canonical function of OAS1 to combat viral and bacterial infections DOI
Marta Martín-Fernández, Dusan Bogunovic

Immunity, Год журнала: 2024, Номер 57(8), С. 1721 - 1723

Опубликована: Авг. 1, 2024

Язык: Английский

Процитировано

0