A Functional Role for TorsinA in Herpes Simplex Virus 1 Nuclear Egress

Martina Maric; Jianqiang Shao; Randi J Ryan; Chun-Shu Wong; Pedro Gonzalez-Alegre; Richard J Roller

doi:10.1128/JVI.05314-11

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A Functional Role for TorsinA in Herpes Simplex Virus 1 Nuclear Egress

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A Functional Role for TorsinA in Herpes Simplex Virus 1 Nuclear Egress

Martina Maric, Jianqiang Shao, Randi J Ryan, Chun-Shu Wong, Pedro Gonzalez-Alegre and Richard J Roller

Journal of virology, Vol.85(19), pp.9667-9679

10/2011

DOI: 10.1128/JVI.05314-11

PMCID: PMC3196446

PMID: 21775450

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Abstract

Herpes simplex virus 1 (HSV-1) capsids leave the nucleus by a process of envelopment and de-envelopment at the nuclear envelope (NE) that is accompanied by structural alterations of the NE. As capsids translocate across the NE, transient primary enveloped virions form in the perinuclear space. Here, we provide evidence that torsinA (TA), a ubiquitously expressed ATPase, has a role in HSV-1 nuclear egress. TA resides within the lumen of the endoplasmic reticulum (ER)/NE and functions in maintaining normal NE architecture. We show that perturbation of TA normal function by overexpressing torsinA wild type (TAwt) inhibits HSV-1 production. Ultrastructural analysis of infected cells overexpressing TAwt revealed reduced levels of surface virions in addition to accumulation of novel, double-membrane structures called virus-like vesicles (VLVs). Although mainly found in the cytoplasm, VLVs resemble primary virions in their size, by the appearance of the inner membrane, and by the presence of pUL34, a structural component of primary virions. Collectively, our data suggest a model in which interference of TA normal function by overexpression impairs de-envelopment of the primary virions leading to their accumulation in a cytoplasmic membrane compartment. This implies novel functions for TA at the NE.

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Title: Subtitle: A Functional Role for TorsinA in Herpes Simplex Virus 1 Nuclear Egress
Creators: Martina Maric - Department of Microbiology, University of Iowa, Iowa City, Iowa 52242
Jianqiang Shao - Central Microscopy Research Facilities, University of Iowa, Iowa City, Iowa 52242
Randi J Ryan - Department of Microbiology, University of Iowa, Iowa City, Iowa 52242
Chun-Shu Wong - Program in Immunology, University of Michigan, Ann Arbor, Michigan 48109
Pedro Gonzalez-Alegre - Department of Neurology, University of Iowa, Iowa City, Iowa 52242
Richard J Roller - Department of Microbiology, University of Iowa, Iowa City, Iowa 52242
Resource Type: Journal article
Publication Details: Journal of virology, Vol.85(19), pp.9667-9679
DOI: 10.1128/JVI.05314-11
PMID: 21775450
PMCID: PMC3196446
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: American Society for Microbiology; 1752 N St., N.W., Washington, DC
Language: English
Date published: 10/2011
Academic Unit: Microbiology and Immunology
Record Identifier: 9984001130202771

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