scholarly journals Trafficking of Varicella-Zoster Virus Glycoprotein gI: T338-Dependent Retention in the trans-Golgi Network, Secretion, and Mannose 6-Phosphate-Inhibitable Uptake of the Ectodomain

2000 ◽  
Vol 74 (14) ◽  
pp. 6600-6613 ◽  
Author(s):  
Zuo-Hong Wang ◽  
Michael D. Gershon ◽  
Octavian Lungu ◽  
Zhenglun Zhu ◽  
Anne A. Gershon
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Fusion Protein ◽  
Varicella Zoster Virus ◽  
Interleukin 2 ◽  
Truncated Protein ◽  
Varicella Zoster ◽  
Virus Glycoprotein ◽  
Mannose 6 Phosphate ◽  
Golgi Network

ABSTRACT The trans-Golgi network (TGN) is putatively the site where varicella-zoster virus is enveloped. gE is targeted to the TGN by selective retrieval from the plasmalemma in response to signaling sequences in its endodomain. gI lacks these sequences but forms a complex with gE. We now find that gI is targeted to the TGN and plasma membrane when expressed in Cos-7 cells; nevertheless, surface labeling revealed that gI is not retrieved from the plasma membrane. TGN targeting of gI depended on the T338 of its endodomain and was lost when T338 was deleted or mutated to A, S, or D. The endodomain of gI was sufficient, if it contained T338, to target a fusion protein containing the ectodomain of the human interleukin-2 receptor to the TGN. A truncated protein consisting only of the gI ectodomain was secreted and taken up by nontransfected cells. This uptake of the secreted gI ectodomain was blocked by mannose 6-phosphate. Following cotransfection, both gI and gE were retrieved to the TGN from the plasma membrane in 26.7% of cells, neither gI nor gE was internalized in 18.3%, and gE was retrieved to the TGN while gI remained at the plasma membrane in 55%. We suggest that the T338 of its endodomain is necessary to retain gI in the TGN; moreover, because gI and gE interact, the signaling sequences of each glycoprotein reinforce one another in ensuring that both glycoproteins are concentrated in the TGN yet remain on the cell surface.

scholarly journals Exocytosis of Progeny Infectious Varicella-Zoster Virus Particles via a Mannose-6-Phosphate Receptor Pathway without Xenophagy following Secondary Envelopment

2020 ◽  
Vol 94 (16) ◽  
Author(s):  
James H. Girsch ◽  
Wallen Jackson ◽  
John E. Carpenter ◽  
Thomas O. Moninger ◽  
Keith W. Jarosinski ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Varicella Zoster Virus ◽  
Melanoma Cells ◽  
Autophagic Flux ◽  
Varicella Zoster ◽  
Late Endosomes ◽  
Viral Particles ◽  
Mannose 6 Phosphate ◽  
Golgi Network ◽  
Infectious Cycle

ABSTRACT The literature on the egress of different herpesviruses after secondary envelopment is contradictory. In this report, we investigated varicella-zoster virus (VZV) egress in a cell line from a child with Pompe disease, a glycogen storage disease caused by a defect in the enzyme required for glycogen digestion. In Pompe cells, both the late autophagy pathway and the mannose-6-phosphate receptor (M6PR) pathway are interrupted. We have postulated that intact autophagic flux is required for higher recoveries of VZV infectivity. To test that hypothesis, we infected Pompe cells and then assessed the VZV infectious cycle. We discovered that the infectious cycle in Pompe cells was remarkably different from that of either fibroblasts or melanoma cells. No large late endosomes filled with VZV particles were observed in Pompe cells; only individual viral particles in small vacuoles were seen. The distribution of the M6PR pathway (trans-Golgi network to late endosomes) was constrained in infected Pompe cells. When cells were analyzed with two different anti-M6PR antibodies, extensive colocalization of the major VZV glycoprotein gE (known to contain M6P residues) and the M6P receptor (M6PR) was documented in the viral highways at the surfaces of non-Pompe cells after maximum-intensity projection of confocal z-stacks, but neither gE nor the M6PR was seen in abundance at the surfaces of infected Pompe cells. Taken together, our results suggested that (i) Pompe cells lack a VZV trafficking pathway within M6PR-positive large endosomes and (ii) most infectious VZV particles in conventional cell substrates are transported via large M6PR-positive vacuoles without degradative xenophagy to the plasma membrane. IMPORTANCE The long-term goal of this research has been to determine why VZV, when grown in cultured cells, invariably is more cell associated and has a lower titer than other alphaherpesviruses, such as herpes simplex virus 1 (HSV1) or pseudorabies virus (PRV). Data from both HSV1 and PRV laboratories have identified a Rab6 secretory pathway for the transport of single enveloped viral particles from the trans-Golgi network within small vacuoles to the plasma membrane. In contrast, after secondary envelopment in fibroblasts or melanoma cells, multiple infectious VZV particles accumulated within large M6PR-positive late endosomes that were not degraded en route to the plasma membrane. We propose that this M6PR pathway is most utilized in VZV infection and least utilized in HSV1 infection, with PRV’s usage being closer to HSV1’s usage. Supportive data from other VZV, PRV, and HSV1 laboratories about evidence for two egress pathways are included.

The varicella zoster virus glycoprotein B (gB) plays a role in virus binding to cell surface heparan sulfate proteoglycans

1998 ◽  
Vol 53 (2) ◽  
pp. 197-207 ◽  
Author(s):  
Alain Jacquet ◽  
Michèle Haumont ◽  
Daya Chellun ◽  
Marc Massaer ◽  
Frank Tufaro ◽  
...  
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Varicella Zoster Virus ◽  
Heparan Sulfate Proteoglycans ◽  
Glycoprotein B ◽  
Virus Binding ◽  
Varicella Zoster ◽  
Virus Glycoprotein

Cell surface expression of the Varicella-zoster virus glycoproteins and Fc receptor

Virology ◽  
1990 ◽  
Vol 178 (1) ◽  
pp. 263-272 ◽  
Author(s):  
Virginia Litwin ◽  
Matyas Sandor ◽  
Charles Grose
Keyword(s):  
Cell Surface ◽  
Varicella Zoster Virus ◽  
Surface Expression ◽  
Fc Receptor ◽  
Cell Surface Expression ◽  
Varicella Zoster

scholarly journals Lysosomal Hydrolase Mannose 6-Phosphate Uncovering Enzyme Resides in the trans-Golgi Network

2001 ◽  
Vol 12 (6) ◽  
pp. 1623-1631 ◽  
Author(s):  
Jack Rohrer ◽  
Rosalind Kornfeld
Keyword(s):  
Plasma Membrane ◽  
Fluorescent Protein ◽  
Lysosomal Hydrolases ◽  
Intracellular Location ◽  
Trans Golgi Network ◽  
Cytosolic Domain ◽  
Cytosolic Domains ◽  
Mannose 6 Phosphate ◽  
Green Fluorescent ◽  
Golgi Network

A crucial step in lysosomal biogenesis is catalyzed by “uncovering” enzyme (UCE), which removes a coveringN-acetylglucosamine from the mannose 6-phosphate (Man-6-P) recognition marker on lysosomal hydrolases. This study shows that UCE resides in the trans-Golgi network (TGN) and cycles between the TGN and plasma membrane. The cytosolic domain of UCE contains two potential endocytosis motifs: 488YHPL and C-terminal 511NPFKD. YHPL is shown to be the more potent of the two in retrieval of UCE from the plasma membrane. A green-fluorescent protein-UCE transmembrane-cytosolic domain fusion protein colocalizes with TGN 46, as does endogenous UCE in HeLa cells, showing that the transmembrane and cytosolic domains determine intracellular location. These data imply that the Man-6-P recognition marker is formed in the TGN, the compartment where Man-6-P receptors bind cargo and are packaged into clathrin-coated vesicles.

scholarly journals Varicella‐Zoster Virus Glycoprotein gE: Endocytosis and Trafficking of the Fc Receptor

1998 ◽  
Vol 178 (s1) ◽  
pp. S2-S6 ◽  
Author(s):  
Julie K. Olson ◽  
Richard A. Santos ◽  
Charles Grose
Keyword(s):  
Varicella Zoster Virus ◽  
Fc Receptor ◽  
Varicella Zoster ◽  
Virus Glycoprotein

scholarly journals Varicella-Zoster Virus Fc Receptor Component gI Is Phosphorylated on Its Endodomain by a Cyclin-Dependent Kinase

1999 ◽  
Vol 73 (2) ◽  
pp. 1320-1330 ◽  
Author(s):  
Ming Ye ◽  
Karen M. Duus ◽  
Junmin Peng ◽  
David H. Price ◽  
Charles Grose
Keyword(s):  
Fusion Protein ◽  
Varicella Zoster Virus ◽  
Phosphorylation Site ◽  
Cytoplasmic Tail ◽  
Casein Kinase Ii ◽  
Fc Receptor ◽  
Casein Kinase ◽  
Cyclin Dependent Kinase ◽  
Varicella Zoster

Varicella-zoster virus (VZV) glycoprotein gI is a type 1 transmembrane glycoprotein which is one component of the heterodimeric gE:gI Fc receptor complex. Like VZV gE, VZV gI was phosphorylated in both VZV-infected cells and gI-transfected cells. Preliminary studies demonstrated that a serine 343-proline 344 sequence located within the gI cytoplasmic tail was the most likely phosphorylation site. To determine which protein kinase catalyzed the gI phosphorylation event, we constructed a fusion protein, consisting of glutathione-S-transferase (GST) and the gI cytoplasmic tail, called GST-gI-wt. When this fusion protein was used as a substrate for gI phosphorylation in vitro, the results demonstrated that GST-gI-wt fusion protein was phosphorylated by a representative cyclin-dependent kinase (CDK) called P-TEFb, a homologue of CDK1 (cdc2). When serine 343 within the serine-proline phosphorylation site was replaced with an alanine residue, the level of phosphorylation of the gI fusion protein was greatly reduced. Subsequent experiments with individually immunoprecipitated mammalian CDKs revealed that the VZV gI fusion protein was phosphorylated best by CDK1, to a lesser degree by CDK2, and not at all by CDK6. Transient-transfection assays carried out in the presence of the specific CDK inhibitor roscovitine strongly supported the prior results by demonstrating a marked decrease in gI phosphorylation while gI protein expression was unaffected. Finally, the possibility that VZV gI contained a CDK phosphorylation site in its endodomain was of further interest because its partner, gE, contains a casein kinase II phosphorylation site in its endodomain; prior studies have established that CDK1 can phosphorylate casein kinase II.

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