Autophagy and the effects of its inhibition on varicella-zoster virus glycoprotein biosynthesis and infectivity

Erin M Buckingham; John E Carpenter; Wallen Jackson; Charles Grose

doi:10.1128/JVI.02646-13

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Autophagy and the effects of its inhibition on varicella-zoster virus glycoprotein biosynthesis and infectivity

Journal article

Open access

Peer reviewed

Autophagy and the effects of its inhibition on varicella-zoster virus glycoprotein biosynthesis and infectivity

Erin M Buckingham, John E Carpenter, Wallen Jackson and Charles Grose

Journal of virology, Vol.88(2), pp.890-902

01/2014

DOI: 10.1128/JVI.02646-13

PMCID: PMC3911683

PMID: 24198400

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Abstract

Autophagy and the effects of its inhibition or induction were investigated during the entire infectious cycle of varicella-zoster virus (VZV), a human herpesvirus. As a baseline, we first enumerated the number of autophagosomes per cell after VZV infection compared with the number after induction of autophagy following serum starvation or treatment with tunicamycin or trehalose. Punctum induction by VZV was similar in degree to punctum induction by trehalose in uninfected cells. Treatment of infected cells with the autophagy inhibitor 3-methyladenine (3-MA) markedly reduced the viral titer, as determined by assays measuring both cell-free virus and infectious foci (P < 0.0001). We next examined a virion-enriched band purified by density gradient sedimentation and observed that treatment with 3-MA decreased the amount of VZV gE, while treatment with trehalose increased the amount of gE in the same band. Because VZV gE is the most abundant glycoprotein, we selected gE as a representative viral glycoprotein. To further investigate the role of autophagy in VZV glycoprotein biosynthesis as well as confirm the results obtained with 3-MA inhibition, we transfected cells with ATG5 small interfering RNA to block autophagosome formation. VZV-induced syncytium formation was markedly reduced by ATG5 knockdown (P < 0.0001). Further, we found that both expression and glycan processing of VZV gE were decreased after ATG5 knockdown, while expression of the nonglycosylated IE62 tegument protein was unchanged. Taken together, our cumulative results not only documented abundant autophagy within VZV-infected cells throughout the infectious cycle but also demonstrated that VZV-induced autophagy facilitated VZV glycoprotein biosynthesis and processing.

Protein Biosynthesis

Viral Envelope Proteins - genetics

Microtubule-Associated Proteins - genetics

Microtubule-Associated Proteins - metabolism

Humans

Chickenpox - metabolism

Autophagy

Herpesvirus 3, Human - genetics

Chickenpox - genetics

Autophagy-Related Protein 5

Virus Replication

Chickenpox - virology

Viral Envelope Proteins - metabolism

Chickenpox - physiopathology

Herpesvirus 3, Human - physiology

Details

Title: Subtitle: Autophagy and the effects of its inhibition on varicella-zoster virus glycoprotein biosynthesis and infectivity
Creators: Erin M Buckingham - Virology Laboratory, University of Iowa Children's Hospital, Iowa City, Iowa, USA
John E Carpenter
Wallen Jackson
Charles Grose
Resource Type: Journal article
Publication Details: Journal of virology, Vol.88(2), pp.890-902
DOI: 10.1128/JVI.02646-13
PMID: 24198400
PMCID: PMC3911683
ISSN: 0022-538X
eISSN: 1098-5514
Grant note: R01 AI089716 / NIAID NIH HHS AI89716 / NIAID NIH HHS
Language: English
Date published: 01/2014
Academic Unit: Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
Record Identifier: 9984093235502771

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