Mobilization of nuclear antiviral factors by Exportin XPO1 via the actin network inhibits RNA virus replication DOI Creative Commons

Biao Sun,

Cheng‐Yu Wu, Paulina Alatriste González

и другие.

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

Опубликована: Дек. 20, 2024

ABSTRACT The intricate interplay between +RNA viruses and their hosts involves the exploitation of host resources to build virus-induced membranous replication organelles (VROs) in cytosol infected cells. Previous genome- proteome-wide approaches have identified numerous nuclear proteins, including restriction factors that affect tomato bushy stunt virus (TBSV). However, it is currently unknown how cells mobilize antiviral proteins tombusviruses manipulate nuclear-cytoplasmic communication. authors discovered XPO1/CRM1 exportin plays a central role TBSV plants. Based on knockdown, chemical inhibition, transient expression vitro experiments, we show XPO1 acts as cellular factor against TBSV. recruited by p33 protein into cytosolic VROs via direct interaction. Blocking nucleocytoplasmic transport function inhibits delivery several resulting dampened effects. co-opted actin network critical for deliver activities. We XPO1-delivered accumulate vir-condensates associated with VROs. Altogether, emerging theme complex: propose vir-condensate serves battleground supremacy controlling infection. It seems balance pro-viral within could be major determining susceptibility. conclude cargos are key players communication during replication. Significance Tomato (TBSV), similar other (+)RNA viruses, replicates exploits organellar membrane surfaces viral represent sites shuttle inhibited conserved interaction nod, which propelled restricted delivered provided inhibitory functions condensates VRO-associated condensate hub implications its

Язык: Английский

Liquid–liquid phase separation in innate immunity DOI
Dawei Liu,

Jinhang Yang,

Ileana M. Cristea

и другие.

Trends in Immunology, Год журнала: 2024, Номер 45(6), С. 454 - 469

Опубликована: Май 17, 2024

Язык: Английский

Процитировано

10
Rational design of phytovirucide inhibiting nucleocapsid protein aggregation in tomato spotted wilt virus DOI Creative Commons
Ningning Zan, Jiao Li, Jiahui Yao

и другие.

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

Опубликована: Фев. 27, 2025

Ineffectiveness of managing plant viruses by chemicals has posed serious challenges in crop production. Recently, phase separation shown to play a key role viral lifecycle. Using inhibitors that can disturb biomolecular condensates formed for virus control been reported medical field. However, the applicability this promising antiviral tactic protection not explored. Here, we report an inhibitor, Z9, targets tomato spotted wilt (TSWV) N protein. Z9 is capable interacting with amino acids nucleic acid binding region TSWV N, disrupting assembly and RNA into phase-separated condensates, reduction which detrimental stability This study provides strategy separation-based control. Biomolecular have recognized as crucial process life cycle. authors inhibitor targeting nucleocapsid protein (N) disrupt its potential

Язык: Английский

Процитировано

1
How do RNA viruses select which RNA to package? The plant virus experience DOI Creative Commons
Hadrien Peyret, Sachin N. Shah,

Yulia Meshcheriakova

и другие.

Virology, Год журнала: 2025, Номер unknown, С. 110435 - 110435

Опубликована: Янв. 1, 2025

The process whereby viral RNA is specifically selected for packaging within particles has been extensively studied over many years. As a result, two broad hypotheses have emerged to explain this specificity, though these are not mutually exclusive. first proposes that the contains specific sequences or "packaging signals" enable it be recognised from mixture of RNAs an infected cell. second suggests there functional coupling between replication and leads only replicating, being packaged. This review aimed at analysing evidence both in vitro vivo studies on positive-strand plant viruses. Overall, seems probable selectivity results rather than presence any sequence. However, also likely signals with high affinity coat protein involved efficient incorporation into particles, thereby favouring correct assembly fully formed infectious particles.

Язык: Английский

Процитировано

1
Plant viruses and biomolecular condensates: novel perspectives in virus replication strategies DOI Open Access
Jared P. May

New Phytologist, Год журнала: 2024, Номер 243(5), С. 1636 - 1638

Опубликована: Апрель 24, 2024

This article is a Commentary on Lin & Nagy (2024), 243 : 1917–1935.

Язык: Английский

Процитировано

5
ER Stress and Viral Defense: Advances and Future Perspectives on Plant Unfolded Protein Response in Pathogenesis DOI Creative Commons
Binita Adhikari, Jeanmarie Verchot, Federica Brandizzí

и другие.

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108354 - 108354

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Screening bacterial effectors and human virus proteins in yeast to identify host factors driving tombusvirus RNA recombination: a role for autophagy and membrane phospholipid content DOI Creative Commons

Judit Pogany,

Jun-ichi Inaba, Yuyan Liu

и другие.

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Май 27, 2025

ABSTRACT Recombination in RNA viruses contributes to virus evolution and rapid emergence of new viral variants that helps evade host’s antiviral strategies. Host factors play important but poorly characterized roles recombination. The authors expressed Legionella bacterium effector proteins SARS-CoV-2 human metapneumovirus (HMPV) yeast test their effects on tomato bushy stunt (TBSV) identified 16 effectors, six SARS-CoV-2, two HMPV affecting TBSV recombination likely target shared host with TBSV. Among the targets effectors/viral was autophagy pathway. Inhibition by expression RavZ LegA9 effectors reduced production recombinants plants. Induction rapamycin, via nitrogen starvation or overexpression ATG2 lipid transfer protein, led enhanced Using vitro replicase assembly giant unilamellar vesicles confirmed critical role phosphatidylethanolamine We suggest pro-recombination co-opted is provide abundant phospholipids for replication organelle biogenesis. Overall, this work highlights membrane context regulation show N M2-1 enhance protecting RNAs from Xrn1 5´−3´ exoribonuclease yeast. Altogether, novel strategy using as a cellular system sensor might assist identification functional various bacterial IMPORTANCE Positive-strand (+)RNA replicate cytosol infected cells exploiting resources frequently lead diseases. Virus results generation contribute adaptation hosts. proteins, This approach revealed heterologous TBSV, including In replication. nucleocapsid protein are shown Thus, TBSV/yeast can be used find functions proteins.

Язык: Английский

Процитировано

0
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
Novel exploitation of autophagy by tombusviruses DOI
Peter D. Nagy,

Judit Pogany,

Yuanrong Kang

и другие.

Virology, Год журнала: 2024, Номер 603, С. 110363 - 110363

Опубликована: Дек. 18, 2024

Язык: Английский

Процитировано

1
RNA-dependent RNA polymerase of predominant human norovirus forms liquid-liquid phase condensates as viral replication factories DOI Creative Commons
Soni Kaundal,

Ramakrishnan Anish,

B. Vijayalakshmi Ayyar

и другие.

Science Advances, Год журнала: 2024, Номер 10(51)

Опубликована: Дек. 20, 2024

Many viral proteins form biomolecular condensates via liquid-liquid phase separation (LLPS) to support replication and evade host antiviral responses, thus, they are potential targets for designing antivirals. In the case of nonenveloped positive-sense RNA viruses, forming such is unclear less understood. Human noroviruses (HuNoVs) viruses that cause epidemic sporadic gastroenteritis worldwide. Here, we show RNA-dependent polymerase (RdRp) pandemic GII.4 HuNoV forms distinct exhibit all signature properties LLPS with sustained activity capability recruiting components essential replication. We formed in HuNoV-infected human intestinal enteroid cultures sites genome Our studies demonstrate formation phase-separated as factories a virus, which plausibly an effective mechanism dynamically isolate RdRp replicating genomic from interfering ribosomal translation same RNA.

Язык: Английский

Процитировано

1
A Vanillin‐Derived Inhibitor of Aggregates via Targeting Intrinsically Disordered Regions of Phytoviral Nucleocapsid Protein DOI Creative Commons
Yanju Wang, Yuqin Luo, Xin Li

и другие.

Aggregate, Год журнала: 2024, Номер unknown

Опубликована: Дек. 22, 2024

ABSTRACT Phase separation (PS) plays a fundamental role in organizing aggregates during the viral lifecycle, providing significant opportunities for disease treatment by inhibiting PS. Intrinsically disordered regions (IDRs) have been extensively studied and found to be critical However, discovery of small molecules that target residues within IDRs remains underexplored, particularly field pesticides. Herein, we report novel phytovirucide compound 29 , which was screened from series vanillin derivatives designed with sulfonylpiperazine motifs. The inactivation efficacy against tomato spotted wilt virus (TSWV) significantly superior control agents vanisulfane ribavirin . Mechanistically, binds TSWV nucleocapsid protein (NP) at Lys68 (K68), Thr92 (T92), Arg94 (R94), T92 R94 located NP. Mutations these sites impair ability form aggregates. Furthermore, host factor, GTP (Guanosine Triphosphate)‐binding nuclear Ran‐like (Niben101scf08341g01001, NbRANL), interacts NP promotes its aggregation, identified. Compound also suppresses expression NbRANL resulting dual inhibition ribonucleoprotein complexes (RNPs) formation. This unique mechanism action provides insights into IDRs‐based virucide discovery.

Язык: Английский

Процитировано

1