ICP0 dismantles microtubule networks in herpes simplex virus-infected cells

Mingyu Liu; Edward E Schmidt; William P Halford

doi:10.1371/journal.pone.0010975

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ICP0 dismantles microtubule networks in herpes simplex virus-infected cells

Journal article

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ICP0 dismantles microtubule networks in herpes simplex virus-infected cells

Mingyu Liu, Edward E Schmidt and William P Halford

PloS one, Vol.5(6), pp.e10975-e10975

06/08/2010

DOI: https://doi.org/10.1371/journal.pone.0010975

Handle:

https://hdl.handle.net/2376/108211

PMCID: PMC2882321

PMID: 20544015

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Abstract

Simplexvirus - physiology

Immediate-Early Proteins - physiology

Humans

Cells, Cultured

Nocodazole - pharmacology

Ubiquitin-Protein Ligases - metabolism

Green Fluorescent Proteins - genetics

Ubiquitin-Protein Ligases - physiology

Protein Transport

Immediate-Early Proteins - metabolism

Microtubules - metabolism

Immediate-Early Proteins - genetics

Virus Replication

Ubiquitin-Protein Ligases - genetics

Infected-cell protein 0 (ICP0) is a RING finger E3 ligase that regulates herpes simplex virus (HSV) mRNA synthesis, and strongly influences the balance between latency and replication of HSV. For 25 years, the nuclear functions of ICP0 have been the subject of intense scrutiny. To obtain new clues about ICP0's mechanism of action, we constructed HSV-1 viruses that expressed GFP-tagged ICP0. To our surprise, both GFP-tagged and wild-type ICP0 were predominantly observed in the cytoplasm of HSV-infected cells. Although ICP0 is exclusively nuclear during the immediate-early phase of HSV infection, further analysis revealed that ICP0 translocated to the cytoplasm during the early phase where it triggered a previously unrecognized process; ICP0 dismantled the microtubule network of the host cell. A RING finger mutant of ICP0 efficiently bundled microtubules, but failed to disperse microtubule bundles. Synthesis of ICP0 proved to be necessary and sufficient to disrupt microtubule networks in HSV-infected and transfected cells. Plant and animal viruses encode many proteins that reorganize microtubules. However, this is the first report of a viral E3 ligase that regulates microtubule stability. Intriguingly, several cellular E3 ligases orchestrate microtubule disassembly and reassembly during mitosis. Our results suggest that ICP0 serves a dual role in the HSV life cycle, acting first as a nuclear regulator of viral mRNA synthesis and acting later, in the cytoplasm, to dismantle the host cell's microtubule network in preparation for virion synthesis and/or egress.

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Title: ICP0 dismantles microtubule networks in herpes simplex virus-infected cells
Creators: Mingyu Liu - Department of Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois, USA
Edward E Schmidt
William P Halford
Publication Details: PloS one, Vol.5(6), pp.e10975-e10975
Academic Unit: UNKNOWN
Publisher: United States
Grant note: R21 AI081072-01A1 / NIAID NIH HHS R21 AI081072 / NIAID NIH HHS R01 AI051414 / NIAID NIH HHS R01 AI51414 / NIAID NIH HHS
Identifiers: 99900547049501842
Language: English
Resource Type: Journal article