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| Content Provider | PubMed Central |
|---|---|
| Author | Liu, Mingyu Schmidt, Edward E. Halford, William P. |
| Editor | Stoddart, Cheryl A. |
| Abstract | 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. |
| Related Links | http://dx.doi.org/10.1371/journal.pone.0010975 |
| Starting Page | 10975 |
| File Format | |
| ISSN | 19326203 |
| e-ISSN | 19326203 |
| Journal | PLoS ONE |
| Issue Number | 6 |
| Volume Number | 5 |
| Language | English |
| Publisher | Public Library of Science |
| Publisher Date | 2010-06-01 |
| Access Restriction | Open |
| Rights Holder | Public Library of Science |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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