The Key to Increase Immunogenicity of Next-Generation COVID-19 Vaccines Lies in the Inclusion of the SARS-CoV-2 Nucleocapsid Protein DOI Creative Commons
Noe Juvenal Mendoza-Ramírez, Julio García‐Cordero, Gaurav Shrivastava

et al.

Journal of Immunology Research, Journal Year: 2024, Volume and Issue: 2024, P. 1 - 18

Published: May 29, 2024

Vaccination is one of the most effective prophylactic public health interventions for prevention infectious diseases such as coronavirus disease (COVID-19). Considering ongoing need new COVID-19 vaccines, it crucial to modify our approach and incorporate more conserved regions severe acute respiratory syndrome 2 (SARS-CoV-2) effectively address emerging viral variants. The nucleocapsid protein a structural SARS-CoV-2 that involved in replication immune responses. Furthermore, this offers significant advantages owing minimal accumulation mutations over time inclusion key T-cell epitopes critical immunity. A novel strategy may be suitable generation vaccines against use combination antigens, including spike proteins, elicit robust humoral potent cellular responses, along with long-lasting strategic multiple antigens aims enhance vaccine efficacy broaden protection viruses, their response from other long-lasting, can persist up 11 years post-infection. Thus, incorporation nucleocapsids (N) into design adds an important dimension vaccination efforts holds promise bolstering ability combat effectively. In review, we summarize preclinical studies evaluated antigen. This study discusses alone its or proteins SARS-CoV-2.

Language: Английский

Cell-Free Expressed Membraneless Organelles Inhibit Translation in Synthetic Cells DOI
Abbey O. Robinson, Jessica Lee,

Anders Cameron

et al.

ACS Biomaterials Science & Engineering, Journal Year: 2024, Volume and Issue: 10(2), P. 773 - 781

Published: Jan. 16, 2024

Compartments within living cells create specialized microenvironments, allowing multiple reactions to be carried out simultaneously and efficiently. While some organelles are bound by a lipid bilayer, others formed liquid-liquid phase separation such as P-granules nucleoli. Synthetic minimal widely used study many natural processes, including organelle formation. In this work, synthetic expressing artificial membrane-less that inhibit translation described. RGG-GFP-RGG, phase-separating protein derived from Caenorhabditis elegans P-granules, is expressed cell-free transcription translation, forming membraneless can sequester RNA reduce expression in cells. The introduction of creates complex microenvironments the cell cytoplasm functions tool engineering compartments furthers understanding evolution function facilitates creation more multifaceted lifelike systems.

Language: Английский

Citations

9
Neurological Diseases can be Regulated by Phase Separation DOI
Colin McCaig

Reviews of physiology, biochemistry and pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 273 - 338

Published: Jan. 1, 2025

Language: Английский

Citations

1
Unstructural Biology of TRP Ion Channels: The Role of Intrinsically Disordered Regions in Channel Function and Regulation DOI
Benedikt Goretzki, Charlotte Guhl, Frederike Tebbe

et al.

Journal of Molecular Biology, Journal Year: 2021, Volume and Issue: 433(17), P. 166931 - 166931

Published: March 18, 2021

Language: Английский

Citations

44
Host casein kinase 1-mediated phosphorylation modulates phase separation of a rhabdovirus phosphoprotein and virus infection DOI Creative Commons
Xiao‐Dong Fang, Qiang Gao, Ying Zang

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Feb. 22, 2022

Liquid-liquid phase separation (LLPS) plays important roles in forming cellular membraneless organelles. However, how host factors regulate LLPS of viral proteins during negative-sense RNA (NSR) virus infection is largely unknown. Here, we used barley yellow striate mosaic (BYSMV) as a model to demonstrate regulation casein kinase 1 (CK1) and NSR viruses. We first found that the BYSMV phosphoprotein (P) formed spherical granules with liquid properties recruited nucleotide (N) polymerase (L) vivo. Moreover, P-formed were tethered ER/actin network for trafficking fusion. P alone droplets incorporated N protein 5′ trailer genomic vitro. Interestingly, was inhibited by CK1-dependent phosphorylation an intrinsically disordered region. Genetic assays demonstrated unphosphorylated mutant exhibited condensed phase, which promoted viroplasm formation replication. Whereas, phosphorylation-mimic existed diffuse state transcription. Collectively, our results CK1 modulates infection.

Language: Английский

Citations

35
Liquid-liquid phase separation of nucleocapsid proteins during SARS-CoV-2 and HIV-1 replication DOI Creative Commons

Bao-An Chau,

Venessa Chen,

Alan Cochrane

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 42(1), P. 111968 - 111968

Published: Dec. 26, 2022

The leap of retroviruses and coronaviruses from animal hosts to humans has led two ongoing pandemics tens millions deaths worldwide. Retrovirus coronavirus nucleocapsid proteins have been studied extensively as potential drug targets due their central roles in virus replication, among which is capacity bind respective genomic RNAs for packaging into nascent virions. This review focuses on fundamental studies these how intrinsic abilities condense through liquid-liquid phase separation (LLPS) contribute viral replication. Therapeutic targeting condensates methodological advances are also described address future questions contributes

Language: Английский

Citations

34
Intrinsically disordered proteins: Ensembles at the limits of Anfinsen's dogma DOI
Prakash Kulkarni,

Vitor B. P. Leite,

Susmita Roy

et al.

Biophysics Reviews, Journal Year: 2022, Volume and Issue: 3(1)

Published: March 1, 2022

Intrinsically disordered proteins (IDPs) are that lack rigid 3D structure. Hence, they often misconceived to present a challenge Anfinsen's dogma. However, IDPs exist as ensembles sample quasi-continuum of rapidly interconverting conformations and, such, may represent at the extreme limit Anfinsen postulate. play important biological roles and key components cellular protein interaction network (PIN). Many can interconvert between ordered states bind appropriate partners. Conformational dynamics contribute conformational noise in cell. Thus, dysregulation contributes increased "promiscuous" interactions. This leads PIN rewiring output an response underscoring critical role decision making. Nonetheless, not easily tractable experimentally. Furthermore, absence reference conformation, discerning energy landscape representation weakly funneled terms reaction coordinates is challenging. To understand real time decipher how recognize multiple binding partners with high specificity, several sophisticated knowledge-based physics-based

Language: Английский

Citations

33
When liquid-liquid phase separation meets viral infections DOI Creative Commons
Wenqiang Wei, Lu Bai, Bing Yan

et al.

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

Published: Aug. 9, 2022

Eukaryotic cells have both membranous and membraneless organelles. While the formation mechanism of organelles is well understood, remains unknown. Many biomolecules in cytoplasm transition from liquid phase to agglutinated are known as liquid-liquid separation (LLPS). The biomolecular agglomerates' physical properties enable them function dynamic compartments that respond external pressures stimuli. Scientists gradually recognized importance during viral infections. LLPS provides a powerful new framework for understanding life cycle replication evasion host immune surveillance. As result, this review focuses on progress research infection regulation provide clues antiviral therapeutic strategies.

Language: Английский

Citations

32
Phase separation in Cancer: From the Impacts and Mechanisms to Treatment potentials DOI Creative Commons
Peng Qiu,

Shiming Tan,

Longzheng Xia

et al.

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(13), P. 5103 - 5122

Published: Jan. 1, 2022

Cancer is a public health problem of great concern, and it also one the main causes death in world.Cancer disease characterized by dysregulation diverse cellular processes, including avoiding growth inhibitory factors, immune damage promoting metastasis, etc.However, precise mechanism tumorigenesis tumor progression still needs to be further elucidated.Formations liquid-liquid phase separation (LLPS) condensates are common strategy for cells achieve functions, such as chromatin organization, signal transduction, DNA repair transcriptional regulation, etc.The biomolecular aggregates formed LLPS mainly driven multivalent weak interactions mediated intrinsic disordered regions (IDRs) proteins.In recent years, aberrant separations transition have been reported related process various diseases, neurodegenerative diseases cancer.Herein, we discussed findings that regulates tumor-related signaling pathways thus contributes progression.We reviewed some virus-associated proteins regulate development tumors via separation.Finally, possible strategies treating targeting separation.

Language: Английский

Citations

32
Host–Pathogen Interactions Influencing Zoonotic Spillover Potential and Transmission in Humans DOI Creative Commons
Beatriz Escudero-Pérez, Alexandre Lalande, Cyrille Mathieu

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(3), P. 599 - 599

Published: Feb. 22, 2023

Emerging infectious diseases of zoonotic origin are an ever-increasing public health risk and economic burden. The factors that determine if when animal virus is able to spill over into the human population with sufficient success achieve ongoing transmission in humans complex dynamic. We currently unable fully predict which pathogens may appear humans, where what impact. In this review, we highlight current knowledge key host–pathogen interactions known influence spillover potential a particular focus on two important viruses origin, Nipah Ebola virus. Namely, determining include cellular tissue tropism, as well virulence pathogenic characteristics pathogen capacity adapt evolve within novel host environment. also detail our emerging understanding importance steric hindrance cell by viral proteins using “flytrap”-type mechanism protein amyloidogenesis could be crucial developing future antiviral therapies against pathogens. Finally, discuss strategies prepare for reduce frequency occurrences order minimize new outbreaks.

Language: Английский

Citations

22
Biomolecular condensates: insights into early and late steps of the HIV-1 replication cycle DOI Creative Commons
Francesca Di Nunzio, Vladimir N. Uversky, Andrew J. Mouland

et al.

Retrovirology, Journal Year: 2023, Volume and Issue: 20(1)

Published: April 7, 2023

Abstract A rapidly evolving understanding of phase separation in the biological and physical sciences has led to redefining virus-engineered replication compartments many viruses with RNA genomes. Condensation viral, host genomic subgenomic RNAs can take place evade innate immunity response help viral replication. Divergent prompt liquid–liquid (LLPS) invade cell. During HIV there are several steps involving LLPS. In this review, we characterize ability individual partners that assemble into biomolecular condensates (BMCs). Of note, bioinformatic analyses predict models line published observations. Importantly, BMCs contribute function key retroviral For example, reverse transcription takes within nuclear BMCs, called HIV-MLOs while during late steps, nucleocapsid acts as a driver or scaffold recruit client components aid assembly progeny virions. Overall, LLPS infections represents newly described event now appreciated virology field, also be considered an alternative pharmacological target current drug therapies especially when become resistant antiviral treatment.

Language: Английский

Citations

21