Vaccinia virus p37 interacts with host proteins associated with LE-derived transport vesicle biogenesis

Chen, Yali; Honeychurch, Kady M.; Yang, Guang; Byrd, Chelsea M.; Harver, Chris; Hruby, Dennis E.; Jordan, Robert

doi:10.1186/1743-422x-6-44

Cited by 62 publications

(53 citation statements)

References 28 publications

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“…Although Retro-2 did not interfere with palmitoylation, it was of interest to determine the effect of the drug on F13 localization. Previous studies had shown that F13 associates with early and late endosomes in addition to the TGN (59,60). Cells were transfected with cytomegalovirus (CMV) vectors expressing TGNP, Rab7, or Rab5 fused to fluorescent tags in order to localize the TGN, late endosomes, and early endosomes, respectively.…”

Section: Resultsmentioning

confidence: 99%

Retrograde Transport from Early Endosomes to the trans -Golgi Network Enables Membrane Wrapping and Egress of Vaccinia Virus Virions

Sivan

Weisberg

Americo

et al. 2016

J Virol

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The anterograde pathway, from the endoplasmic reticulum through the trans-Golgi network to the cell surface, is utilized by trans-membrane and secretory proteins. The retrograde pathway, which directs traffic in the opposite direction, is used following endocytosis of exogenous molecules and recycling of membrane proteins. Microbes exploit both routes: viruses typically use the anterograde pathway for envelope formation prior to exiting the cell, whereas ricin and Shiga-like toxins and some nonenveloped viruses use the retrograde pathway for cell entry. Mining a human genome-wide RNA interference (RNAi) screen revealed a need for multiple retrograde pathway components for cell-to-cell spread of vaccinia virus. We confirmed and extended these results while discovering that retrograde trafficking was required for virus egress rather than entry. Retro-2, a specific retrograde trafficking inhibitor of protein toxins, potently prevented spread of vaccinia virus as well as monkeypox virus, a human pathogen. Electron and confocal microscopy studies revealed that Retro-2 prevented wrapping of virions with an additional double-membrane envelope that enables microtubular transport, exocytosis, and actin polymerization. The viral B5 and F13 protein components of this membrane, which are required for wrapping, normally colocalize in the trans-Golgi network. However, only B5 traffics through the secretory pathway, suggesting that F13 uses another route to the trans-Golgi network. The retrograde route was demonstrated by finding that F13 was largely confined to early endosomes and failed to colocalize with B5 in the presence of Retro-2. Thus, vaccinia virus makes novel use of the retrograde transport system for formation of the viral wrapping membrane. IMPORTANCEEfficient cell-to-cell spread of vaccinia virus and other orthopoxviruses depends on the wrapping of infectious particles with a double membrane that enables microtubular transport, exocytosis, and actin polymerization. Interference with wrapping or subsequent steps results in severe attenuation of the virus. Some previous studies had suggested that the wrapping membrane arises from the trans-Golgi network, whereas others suggested an origin from early endosomes. Some nonenveloped viruses use retrograde trafficking for entry into the cell. In contrast, we provided evidence that retrograde transport from early endosomes to the trans-Golgi network is required for the membrane-wrapping step in morphogenesis of vaccinia virus and egress from the cell. The potent in vitro inhibition of this step by the drug Retro-2 suggests that derivatives with enhanced pharmacological properties might serve as useful antipoxviral agents. V accinia virus (VACV) is the prototype member of the poxvirus family of cytoplasmic double-stranded DNA viruses (1). The first infectious form of VACV, the intracellular mature virion (MV), is a brick-shaped particle consisting of a nucleoprotein core, lateral bodies, and a surrounding lipoprotein membrane (2). A subset of cytoplasmic MVs are wr...

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Section: Resultsmentioning

confidence: 99%

Retrograde Transport from Early Endosomes to the trans -Golgi Network Enables Membrane Wrapping and Egress of Vaccinia Virus Virions

Sivan

Weisberg

Americo

et al. 2016

J Virol

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“…Data from these time points confirmed that the fusion protein accumulated in the same fractions as reported previously. Several wellstudied plant and animal viruses have been shown to relocate host proteins by altering signals on endomembranes (7,11,32,34,36). It is possible that CHV1 factors present in the vesicles alter their original destination.…”

Section: Figmentioning

confidence: 99%

The Mycovirus CHV1 Disrupts Secretion of a Developmentally Regulated Protein in Cryphonectria parasitica

Kazmierczak

McCabe²,

Turina

et al. 2012

J Virol

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Infection of the chestnut blight fungus Cryphonectria parasitica with Cryphonectria hypovirus 1 (CHV1) causes disruption of virulence, pigmentation, and sporulation. Transcriptional downregulation of key developmentally regulated fungal genes occurs during infection, but vegetative growth is unaffected. Previous studies showed that CHV1 utilizes trans -Golgi network (TGN) secretory vesicles for replication. In this study, the fungal cell surface hydrophobin cryparin was chosen as a marker to follow secretion in virally infected and noninfected strains. Subcellular fractionation, cryparin-green fluorescent protein (GFP) fusion, and Western blot studies confirmed that vesicles containing cryparin copurify with the same fractions previously shown to contain elements of the viral replication complex and the TGN resident endoprotease Kex2. This vesicle fraction accumulated to a much greater concentration in the CHV1-infected strains than in noninfected strains. Pulse-chase analysis showed that the rates and amount of cryparin being secreted by the CHV1 containing strains was much lower than in noninfected strains, and the dwell time of cryparin within the cell after labeling was significantly greater in the CHV1-infected strains than in the noninfected ones. These results suggest that the virus perturbs a specific late TGN secretory pathway resulting in buildup of a key protein important for fungal development.

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“…Because TIP47 is also involved in lipid droplet biogenesis under conditions of rapid fat storage, it remains to be determined if TIP47 might be a shared effector that also interacts with one of the myriad of Rab GTPases involved in lipid droplet formation or, alternatively, promotes interorganellar tethering to lipid droplets to allow access to critical lipid regulators of endocytosis Bulankina et al 2009;Hynson et al 2012). Indeed, Tip47 and Rab9 are important targets in viral infectivity and have been associated with lipid droplet consumption, suggesting that resolving this open question will be of significant interest (Murray et al 2005;Chen et al 2009b;Carvalho et al 2012;Vogt et al 2013). Based on the cumulative evidence, it is speculated that Rab-mediated cargo selection and vesicle budding will involve specific lipid recruitment through cis or trans membrane interactions, signal-dependent cargo binding, cooperativity between Arf and Rab GTPases, and GTPase regulatory factors for spatiotemporal control of protein -protein interactions.…”

Section: Rab Gtpases In Vesicle Buddingmentioning

confidence: 99%

Rab Proteins and the Compartmentalization of the Endosomal System

Wandinger‐Ness

Zerial

2014

Cold Spring Harbor Perspectives in Biology

505

469

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Of the approximately 70 human Rab GTPases, nearly three-quarters are involved in endocytic trafficking. Significant plasticity in endosomal membrane transport pathways is closely coupled to receptor signaling and Rab GTPase-regulated scaffolds. Here we review current literature pertaining to endocytic Rab GTPase localizations, functions, and coordination with regulatory proteins and effectors. The roles of Rab GTPases in (1) compartmentalization of the endocytic pathway into early, recycling, late, and lysosomal routes; (2) coordination of individual transport steps from vesicle budding to fusion; (3) effector interactomes; and (4) integration of GTPase and signaling cascades are discussed.

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Vaccinia virus p37 interacts with host proteins associated with LE-derived transport vesicle biogenesis

Cited by 62 publications

References 28 publications

Retrograde Transport from Early Endosomes to the trans -Golgi Network Enables Membrane Wrapping and Egress of Vaccinia Virus Virions

Retrograde Transport from Early Endosomes to the trans -Golgi Network Enables Membrane Wrapping and Egress of Vaccinia Virus Virions

The Mycovirus CHV1 Disrupts Secretion of a Developmentally Regulated Protein in Cryphonectria parasitica

Rab Proteins and the Compartmentalization of the Endosomal System

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