Influenza A virus-induced production of PI4P at the endoplasmic reticulum involves ATG16L1 and promotes the egress of viral ribonucleoproteins DOI Creative Commons

Carla Alemany,

Juliane Da Graça, Quentin Giai Gianetto

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 30, 2024

The genomic RNAs of influenza A viruses (IAVs) are replicated in the nucleus infected cells form viral ribonucleoproteins (vRNP) before being exported to cytoplasm. small GTPase RAB11A is involved transport vRNPs sites assembly at plasma membrane, but molecular mechanisms remain largely unknown. Here we show that IAV infection remodels architecture endoplasmic reticulum (ER) sheets, where tend accumulate absence RAB11A. To decipher interplay between RAB11A, and ER, investigated viral-induced perturbations proximity interactome. this end, generated stably expressing a TurboID-RAB11A fusion protein performed biotin-based labeling upon infection. We found cellular regulators phophatidylinositol-4-phosphate (PI4P) homeostasis, including autophagic stress response ATG16L1, significantly enriched vicinity cells. Infection induces an increase PI4P levels ATG16L1-dependent manner, while ATG16L1 relocalizes ER membranes Depletion decreases co-distribution with punctae on membranes, reduces accumulation membrane as well production infectious particles. Our data extend IAVs notion can modulate metabolism localization phosphoinositides control host dynamics point essential platform for vRNP transport. They provide evidence pivotal role regulating identity endomembranes coordinating PI4P-enriched ensure delivery membrane.

Язык: Английский

The Influenza A Virus Replication Cycle: A Comprehensive Review DOI Creative Commons
Toby Carter, Munir Iqbal

Viruses, Год журнала: 2024, Номер 16(2), С. 316 - 316

Опубликована: Фев. 19, 2024

Influenza A virus (IAV) is the primary causative agent of influenza, colloquially called flu. Each year, it infects up to a billion people, resulting in hundreds thousands human deaths, and causes devastating avian outbreaks with worldwide losses worth billions dollars. Always present possibility that highly pathogenic novel subtype capable direct human-to-human transmission will spill over into humans, causing pandemic as if not more so than 1918 influenza pandemic. While antiviral drugs for do exist, they target very few aspects IAV replication risk becoming obsolete due resistance. Antivirals targeting other areas are needed overcome this resistance combat yearly epidemics, which exact serious toll worldwide. This review aims summarise key steps cycle, along highlighting research need focus.

Язык: Английский

Процитировано

20
Emerging roles of ATG9/ATG9A in autophagy: implications for cell and neurobiology DOI Creative Commons
Ji-Young Choi,

Haeun Jang,

Xuan Zhao

и другие.

Autophagy, Год журнала: 2024, Номер 20(11), С. 2373 - 2387

Опубликована: Авг. 4, 2024

Atg9, the only transmembrane protein among many autophagy-related proteins, was first identified in year 2000 yeast. Two homologs of ATG9A and ATG9B, have been found mammals. While ATG9B shows a tissue-specific expression pattern, such as placenta pituitary gland, is ubiquitously expressed. Additionally, deficiency leads to severe defects not at molecular cellular levels but also organismal level, suggesting key fundamental roles for ATG9A. The subcellular localization on small vesicles its functional relevance autophagy suggested potential role lipid supply during autophagosome biogenesis. Nevertheless, precise autophagic process has remained long-standing mystery, especially neurons. Recent findings, however, including structural, proteomic, biochemical analyses, provided new insights into function expansion phagophore membrane. In this review, we aim understand various aspects ATG9 (in invertebrates plants)/ATG9A mammals), localization, trafficking, other functions, nonneuronal cells neurons by comparing recent discoveries related ATG9/ATG9A proposing directions future research.

Язык: Английский

Процитировано

5
Fluorescence Loss After Photoactivation (FLAPh): A Pulse-Chase Cellular Assay for Understanding Kinetics and Dynamics of Viral Inclusions DOI
Temitope Akhigbe Etibor, Tiago Paixão, Maria João Amorim

и другие.

Methods in molecular biology, Год журнала: 2025, Номер unknown, С. 125 - 140

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Trafficking of K63-polyubiquitin modified membrane proteins in a macroautophagy-independent pathway is linked to ATG9A DOI Open Access
Francesco Scavone,

Sharon Lian,

Eeva‐Liisa Eskelinen

и другие.

Molecular Biology of the Cell, Год журнала: 2025, Номер 36(4)

Опубликована: Фев. 19, 2025

Cytoplasmic K63-linked polyubiquitin signals have well-established roles in endocytosis and selective autophagy. However, how these help to direct different cargos intracellular trafficking routes is unclear. Here we report that, when the K63-polyubiquitin signal blocked by expression of a high-affinity sensor (named Vx3), many proteins originating from plasma membrane are found trapped clusters small vesicles that colocalize with ATG9A, transmembrane protein plays an essential role Importantly, whereas ATG9A required for cluster formation, other core autophagy machinery as well cargo receptors not required. Although sequestered vesicular ATG9-dependent manner, additional needed induce LC3 conjugation. Upon removal Vx3 block, K63-polyubiquitylated rapidly delivered lysosomes. These observations suggest unexpected K63-polyubiquitin–modified proteins.

Язык: Английский

Процитировано

0
Influenza A virus RNA localisation and the interceding trafficking pathways of the host cell DOI Creative Commons
Stefano Bonazza, David G. Courtney

PLoS Pathogens, Год журнала: 2025, Номер 21(4), С. e1013090 - e1013090

Опубликована: Апрель 23, 2025

Viruses have evolved to efficiently navigate host cells deliver, express, and replicate their genetic material. Understanding the mechanisms underlying viral RNA localisation is paramount designing new antivirals. In this review, we discuss Influenza A Virus (IAV) as a model system highlight some of ways in which viruses can hijack endomembrane systems, well nuclear transporters, achieve correct transcripts. IAV exemplifies nuclear-replicating virus with complex highly regulated trafficking within cells. The subverts various vesicular transport systems altering normal cellular functions. begins during entry; after clathrin-mediated endocytosis, genome (vRNPs) released into cytosol fusion endosomal membrane, it subsequently imported nucleus via importin system. There, vRNPs engage most major subnuclear structures exploit chromatin, transcription machinery splicing apparatus efficient mRNA synthesis export. Subsequently, newly synthesised are rapidly exported from contact host’s recycling endosome network for plasma membrane. We critical remodelling entire system, particularly Rab11 endoplasmic reticulum. Lastly, replicated genomes come together bundles be inserted budding virions, current models being proposed evidence behind them. Despite advances understanding these processes, several knowledge gaps remain, regarding specific export unspliced transcripts, segment bundling.

Язык: Английский

Процитировано

0
Myoferlin is an essential component of late-stage vRNP trafficking vesicles for enveloped RNA viruses. DOI
Stefano Bonazza,

Hannah L. Turkington,

Hannah L Coutts

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 2, 2024

Abstract The Rab11a endosomal recycling pathway is exploited by important respiratory RNA viruses such as IAV and RSV, aiding viral egress from the apical surface of polarized epithelial cells. Late in infection, Rab11a-containing vesicles specifically transport ribonucleoprotein (vRNP) complexes towards cell before packaging budding. Rather than employing traditional Rab11a-positive endosomes, virus-infected cells generate remodelled vesicles, observed during infection. Besides Rab11a, no other conserved host co-factors have been identified among these various vRNP trafficking vesicles. Here we discovered confirmed myoferlin’s association with vRNPs cytoplasm colocalisation late stages We also found that this role was late-stage viruses, including RSV SeV. Myoferlin likely recruits EHD family proteins, which are involved biogenesis, to unique highlighting pivotal replication.

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
The cold-inducible RNA-binding protein RBM3 stabilises viral mRNA at the cooler temperatures of the upper respiratory tract DOI Creative Commons
Hannah L Coutts,

Hannah L. Turkington,

Stefano Bonazza

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 25, 2024

Abstract Temperature regulation is a key aspect of homeostasis, and several systems are involved in orchestrating adjustments gene expression at the cellular level. One such factor RBM3, cold-inducible RNA-binding protein implicated aspects mRNA processing regulation. The upper respiratory tract serves as unique environment regarding temperature Physiologically, lower relatively stable 37°C, while fluctuates or below 33°C. Adapting to this differential, subsequent differences transcriptome proteome, essential for viruses that infect cause disease simultaneously replicating transmitting from tract. At present, our understanding molecular mechanisms underlying influenza virus infection cooler temperatures lacking. Unsurprisingly, RBM3 levels highest nasopharyngeal tissue. Coupled with its known role positively regulating bound RNA, it an appealing candidate manipulation by viruses. We found siRNA knockdown significantly decreased viral replication. To disentangle direct effect RMB3 shift global colder temperatures, we generated A549 cell line constitutively overexpressing 37°C. Overexpression resulted significant increase was readily bind NP during prolong half-life these transcripts. In contrast, RNA binding null mutant reverses phenotype, validating interaction has stabilising on proviral nature increased further validated more clinically relevant model well-differentiated primary nasal epithelial cells. These data suggest supporting replication Understanding IAV could prove fundamental elucidating transmission reassortment. Author Summary establish productive infection, must overcome adapt within body. obstacle gradient tract, which route transmission, provides drastically different compared due growth temperatures. Here, detail investigation into (RBP) landscape between 33°C Our aim identify specific RBPs upregulated explore their A (IAV) lifecycle, thereby advancing knowledge Through combination virology mass spectrometry, identified RBP, important post-transcriptional regulator nucleoprotein (NP) mRNA. show binds specifically mRNA, ultimately promoting production infectious virions, abolishing capabilities reversed effect. Overall, find enhanced seen influences

Язык: Английский

Процитировано

0
Influenza A virus-induced production of PI4P at the endoplasmic reticulum involves ATG16L1 and promotes the egress of viral ribonucleoproteins DOI Creative Commons

Carla Alemany,

Juliane Da Graça, Quentin Giai Gianetto

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 30, 2024

The genomic RNAs of influenza A viruses (IAVs) are replicated in the nucleus infected cells form viral ribonucleoproteins (vRNP) before being exported to cytoplasm. small GTPase RAB11A is involved transport vRNPs sites assembly at plasma membrane, but molecular mechanisms remain largely unknown. Here we show that IAV infection remodels architecture endoplasmic reticulum (ER) sheets, where tend accumulate absence RAB11A. To decipher interplay between RAB11A, and ER, investigated viral-induced perturbations proximity interactome. this end, generated stably expressing a TurboID-RAB11A fusion protein performed biotin-based labeling upon infection. We found cellular regulators phophatidylinositol-4-phosphate (PI4P) homeostasis, including autophagic stress response ATG16L1, significantly enriched vicinity cells. Infection induces an increase PI4P levels ATG16L1-dependent manner, while ATG16L1 relocalizes ER membranes Depletion decreases co-distribution with punctae on membranes, reduces accumulation membrane as well production infectious particles. Our data extend IAVs notion can modulate metabolism localization phosphoinositides control host dynamics point essential platform for vRNP transport. They provide evidence pivotal role regulating identity endomembranes coordinating PI4P-enriched ensure delivery membrane.

Язык: Английский

Процитировано

0