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

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 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

Language: Английский

VPS13 and bridge-like lipid transporters, mechanisms, and mysteries DOI Creative Commons
Laura E. Swan

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: April 28, 2025

Bridge-like lipid transporters (BLTPs) have recently been revealed as key regulators of intraorganellar trafficking, with their loss being associated defective synaptic signalling and congenital neurological diseases. This group consists five protein subfamilies [BLTP1-3, autophagy-related 2 (ATG2), vacuolar sorting 13 (VPS13)], which mediate minimally selective transfer between cellular membranes. Deceptively simple in both structure presumed function, this review addresses open questions to how bridge-like work, the functional consequences bulk on signalling, summarises some recent studies that shed light surprising level regulation specificity found family transporters.

Language: Английский

Citations

0
Co-opted ATG2 lipid transfer protein delivers phospholipids for biogenesis of viral replication organelles DOI Creative Commons
Yuanrong Kang,

Judit Pogany,

Peter D. Nagy

et al.

Autophagy Reports, Journal Year: 2024, Volume and Issue: 3(1)

Published: Dec. 1, 2024

Positive-strand RNA viruses, which are important pathogens of humans, animals and plants, subvert cellular membranes induce de novo membrane proliferation to generate viral replication organelles (VROs) that support virus replication. Tomato bushy stunt (TBSV), an extensively-studied plant replicating in yeast model host hijacks ATG2 (autophagy-related 2), a lipid transfer protein (LTP) transports lipids between adjacent at contact sites, for the biogenesis their membranous VROs. Subversion by TBSV is enrich VRO with phosphatidylethanolamine (PE), phosphatidylserine (PS) phosphoinositide phosphatidylinositol-3-phosphate [PI(3)P], all required directly interacts leading recruitment independently autophagy machinery.

Language: Английский

Citations

1
Novel exploitation of autophagy by tombusviruses DOI
Peter D. Nagy,

Judit Pogany,

Yuanrong Kang

et al.

Virology, Journal Year: 2024, Volume and Issue: 603, P. 110363 - 110363

Published: Dec. 18, 2024

Language: Английский

Citations

0
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

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 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

Language: Английский

Citations

0