ATG9A regulates dissociation of recycling endosomes from microtubules leading to formation of influenza A virus liquid condensates DOI Creative Commons
Sílvia Vale-Costa, Temitope Akhigbe Etibor, Daniela Brás

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Дек. 22, 2022

ABSTRACT It is now established that many viruses threaten public health establish condensates via phase transitions to complete their lifecycles, and knowledge on such processes may offer new strategies for antiviral therapy. In the case of influenza A virus (IAV), liquid known as viral inclusions, concentrate 8 distinct ribonucleoproteins (vRNPs) form IAV genome are viewed sites dedicated assembly 8-partite genomic complex. Despite not being delimited by host membranes, inclusions accumulate membranes inside a result vRNP binding recycling endocytic marker Rab11a, driver biogenesis these structures. We lack molecular understanding how Rab11a-recycling endosomes condensate specifically near endoplasmic reticulum (ER) exit upon infection. show here interact with ER fuse, divide slide. uncover that, contrary previous indications, reported reduction in activity regulated process rather than competition cellular resources involving novel role factor ATG9A. infection, ATG9A mediates removal carrying vRNPs from microtubules. observe usage microtubules rescued when depleted, which prevents condensation Rab11a ER. The failure produce accumulates cytosol, reduces release infectious virions. propose supports dynamics facilitating formation. This work advances our epidemic pandemic genomes formed. also reveals plasticity pathway undergo response disclosing roles beyond its classical involvement autophagy.

Язык: Английский

Localising enzymes to biomolecular condensates increases their accumulation and benefits engineered metabolic pathway performance in Nicotiana benthamiana DOI Creative Commons
Anya Lindström Battle, A. John Barrett, Mark D. Fricker

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

Summary Establishment of N. benthamiana as a robust biofactory is complicated by issues such product toxicity and proteolytic degradation target proteins / introduced enzymes. Here we investigate whether biomolecular condensates can be used to address these problems. We engineered in leaves using transient expression synthetic modular scaffolds. The vivo properties the that resulted were consistent with them being liquid-like bodies thermodynamic features typical multicomponent phase-separating systems. show recruitment enzymes led several fold yield increases one- three-step metabolic pathways (citramalate biosynthesis poly-3-hydroxybutyrate (PHB) biosynthesis, respectively). This enhanced could for reasons including improved enzyme kinetics, metabolite channelling or avoidance cytotoxicity retention pathway within condensate, which was demonstrated PHB. However, also observed several-fold increase amount accumulated when they targeted condensates. suggests more stable localised condensate than freely diffusing cytosol. hypothesise this stability likely main driver increased production. Our findings provide foundation leveraging plant engineering advance versatile industrial applications.

Язык: Английский

Процитировано

0
Localising enzymes to biomolecular condensates increase their accumulation and benefits engineered metabolic pathway performance in Nicotiana benthamiana DOI Creative Commons
Anya Lindström Battle, A. John Barrett, Mark D. Fricker

и другие.

Plant Biotechnology Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Summary The establishment of Nicotiana benthamiana as a robust biofactory is complicated by issues such product toxicity and proteolytic degradation target proteins/introduced enzymes. Here we investigate whether biomolecular condensates can be used to address these problems. We engineered in N. leaves using transient expression synthetic modular scaffolds. vivo properties the that resulted were consistent with them being liquid‐like bodies thermodynamic features typical multicomponent phase‐separating systems. show recruitment enzymes led several‐fold yield increases one‐ three‐step metabolic pathways (citramalate biosynthesis poly‐3‐hydroxybutyrate (PHB) biosynthesis, respectively). This enhanced could for several reasons including improved enzyme kinetics, metabolite channelling or avoidance cytotoxicity retention pathway within condensate, which was demonstrated PHB. However, also observed increase amount accumulated when they targeted condensates. suggests more stable localised condensate than freely diffusing cytosol. hypothesise this stability likely main driver increased production. Our findings provide foundation leveraging plant engineering advance versatile industrial applications.

Язык: Английский

Процитировано

0
O-GlcNAcylation reduces proteome solubility and regulates the formation of biomolecular condensates in human cells DOI Creative Commons
Senhan Xu, Kejun Yin, Xing Xu

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 30, 2025

O-GlcNAcylation plays critical roles in the regulation of protein functions and cellular activities, including interactions with other macromolecules. While formation biomolecular condensates (or biocondensates) regulated by a few individual proteins has been reported, systematic investigation on biocondensate remains to be explored. Here we systematically study regulating solubility its impacts RNA-protein using mass spectrometry-based chemoproteomics. Unexpectedly, observe system-wide decrease modified O-GlcNAcylation, glycoproteins involved focal adhesion actin binding exhibiting most significant decrease. Furthermore, sites located disordered regions fewer acidic aromatic residues nearby are related greater drop solubility. Additionally, discover that specific group events promotes dissociation under heat stress, while some enhance during recovery phase. Using site mutagenesis, inhibition O-GlcNAc transferase, fluorescence microscopy, validate regulates biocondensates for YTHDF3 NUFIP2. This work advances our understanding condensates.

Язык: Английский

Процитировано

0
Fast and flu-rious: How to prevent and treat emerging influenza A viruses DOI Creative Commons

Isabel Sesifredo,

Íris L. Batalha, Maria João Amorim

и другие.

PLoS Pathogens, Год журнала: 2025, Номер 21(5), С. e1013135 - e1013135

Опубликована: Май 16, 2025

Язык: Английский

Процитировано

0
Nonviral protein cages as tools to decipher and combat viral threats DOI Creative Commons
Mikail D. Levasseur

npj Viruses, Год журнала: 2025, Номер 3(1)

Опубликована: Май 26, 2025

Zoonotic viruses rank among the greatest threats to public health, with urbanization and global warming accelerating their emergence spread. As risk of future pandemics grows, innovative tools are needed deepen our understanding viral pathogenesis enhance pandemic preparedness. Nonviral protein cages provide a versatile platform for studying mechanisms, virus-host interactions, designing next-generation therapeutic approaches, making them powerful assets in fight against threats.

Язык: Английский

Процитировано

0
Influenza A virus propagation requires the activation of the unfolded protein response and the accumulation of insoluble protein aggregates DOI Creative Commons
Mariana Marques, Bruno Ramos, Hélio M. T. Albuquerque

и другие.

iScience, Год журнала: 2024, Номер 27(3), С. 109100 - 109100

Опубликована: Фев. 2, 2024

Influenza A virus (IAV) employs multiple strategies to manipulate cellular mechanisms and support proper virion formation propagation. In this study, we performed a detailed analysis of the interplay between IAV host cells' proteostasis throughout entire infectious cycle. We reveal that infection activates inositol requiring enzyme 1 (IRE1) branch unfolded protein response, activation is important for an efficient infection. further observed accumulation virus-induced insoluble aggregates, containing both viral proteins, associated with dysregulation cell RNA metabolism. Our data indicate propagation favors final steps cycle, more specifically assembly. These findings additional by which disrupts uncovers new targets can be explored development host-directed antiviral strategies.

Язык: Английский

Процитировано

2
Unraveling Liquid–Liquid Phase Separation (LLPS) in Viral Infections to Understand and Treat Viral Diseases DOI Open Access
Marie Galloux, Sonia Longhi

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 6981 - 6981

Опубликована: Июнь 26, 2024

In the field of virology, liquid-liquid phase separation (LLPS) has emerged as a pivotal mechanism enabling compartmentalization required for specific steps viral replication cycle [...].

Язык: Английский

Процитировано

1
Liquid-liquid phase separation in viral infection: from the occurrence and function to treatment potentials DOI
Zheng Cao,

Yanhua Yang,

Simeng Zhang

и другие.

Colloids and Surfaces B Biointerfaces, Год журнала: 2024, Номер 246, С. 114385 - 114385

Опубликована: Ноя. 17, 2024

Язык: Английский

Процитировано

1
Biomolecular condensates: phasing in regulated host–pathogen interactions DOI
Kun Chen, Xuetao Cao

Trends in Immunology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

Процитировано

1
Influenza A virus activates the unfolded protein response and induces the accumulation of insoluble protein aggregates that are essential for efficient viral propagation DOI Creative Commons
Mariana Marques, Bruno Ramos, Hélio M. T. Albuquerque

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 11, 2023

Abstract Influenza A virus (IAV) is one of the main causes annual respiratory epidemics in humans. IAV employs multiple strategies to evade host immunity and hijack cellular mechanisms support proper virion formation propagation. Some these encompass manipulation pathways involved protein homeostasis, leading changes proteome distribution within cell. In this study, we performed a detailed analysis interplay between cells’ proteostasis throughout entire infectious cycle. We reveal that infection induces activation inositol requiring enzyme 1 (IRE1) branch unfolded response (UPR), at an stage coincides with high rates viral translation. This particularly important for infection, as attenuation production was observed upon IRE1 inhibition. Concomitantly UPR activation, accumulation virus-induced insoluble aggregates, which contain both proteins are associated dysregulation cell RNA metabolism. demonstrate propagation, its prevention using quinoline-steroid hybrid compound significantly reduces number produced particles. Our data suggests aggregates favors final steps cycle, more specifically assembly. findings additional by disrupts favor uncover new targets can be explored development host-directed antiviral strategies.

Язык: Английский

Процитировано

1