Insulin-Degrading Enzyme Binds to the Nonglycosylated Precursor of Varicella-Zoster Virus gE Protein Found in the Endoplasmic Reticulum

J. E Carpenter; W Jackson; G. A de Souza; L Haarr; C Grose

doi:10.1128/JVI.01801-09

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Insulin-Degrading Enzyme Binds to the Nonglycosylated Precursor of Varicella-Zoster Virus gE Protein Found in the Endoplasmic Reticulum

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Insulin-Degrading Enzyme Binds to the Nonglycosylated Precursor of Varicella-Zoster Virus gE Protein Found in the Endoplasmic Reticulum

J. E Carpenter, W Jackson, G. A de Souza, L Haarr and C Grose

Journal of virology, Vol.84(2), pp.847-855

01/2010

DOI: 10.1128/JVI.01801-09

PMCID: PMC2798375

PMID: 19864391

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Abstract

Insulin degradation enzyme (IDE) is a 110-kDa zinc metalloprotease found in the cytosol of all cells. IDE degrades insulin and a variety of small proteins including amyloid-β. Recently, IDE has been proposed as the receptor for varicella-zoster virus (VZV) attachment. During our reassessment, some of the original studies were repeated and expanded in scope. We first confirmed that IDE antibody reduced VZV spread. For additional controls, we repeated the same experiments with herpes simplex virus (HSV)-infected cells as well as uninfected cells. There was a visible reduction in HSV spread but less than seen in the VZV system. Of greater importance, IDE antibody also inhibited the growth of uninfected cells. Second, we repeated the coprecipitation assays. We confirmed that antibodies to VZV gE (open reading frame 68) coprecipitated IDE and that anti-IDE antibody coprecipitated gE. However, the detected gE protein was not the mature 98-kDa form; rather, it was a precursor 73-kDa gE form found in the endoplasmic reticulum. Additional control experiments included VZV-infected cell cultures treated with tunicamycin to block gE glycosylation in the endoplasmic reticulum; again, the anti-IDE antibody coprecipitated a 73-kDa gE product. Finally, Orbitrap mass spectrometry analysis of a chromatographically purified gE sample revealed four cellular proteins associated with the unfolded protein response: BiP (HSPA5), HSPA8, HSPD1, and PPIA (peptidyl-propyl cis - trans isomerase). We conclude that IDE protease binds to the 73-kDa gE precursor and that this event occurs in the cytosol but not as a receptor/ligand interaction.

Virus-Cell Interactions

Details

Title: Subtitle: Insulin-Degrading Enzyme Binds to the Nonglycosylated Precursor of Varicella-Zoster Virus gE Protein Found in the Endoplasmic Reticulum
Creators: J. E Carpenter - Children's Hospital, University of Iowa, Iowa City, Iowa
W Jackson - Children's Hospital, University of Iowa, Iowa City, Iowa
G. A de Souza - Children's Hospital, University of Iowa, Iowa City, Iowa
L Haarr - Children's Hospital, University of Iowa, Iowa City, Iowa
C Grose - Children's Hospital, University of Iowa, Iowa City, Iowa
Resource Type: Journal article
Publication Details: Journal of virology, Vol.84(2), pp.847-855
DOI: 10.1128/JVI.01801-09
PMID: 19864391
PMCID: PMC2798375
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: American Society for Microbiology (ASM)
Language: English
Date published: 01/2010
Academic Unit: Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
Record Identifier: 9984093212202771

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