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The Human Polyoma JC Virus Agnoprotein Acts as a Viroporin
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| Title: | The Human Polyoma JC Virus Agnoprotein Acts as a Viroporin |
| Authors: | Suzuki, Tadaki Browse this author | | Orba, Yasuko Browse this author | | Okada, Yuki Browse this author | | Sunden, Yuji Browse this author | | Kimura, Takashi Browse this author | | Tanaka, Shinya Browse this author →KAKEN DB | | Nagashima, Kazuo Browse this author | | Hall, William W. Browse this author | | Sawa, Hirofumi Browse this author |
| Issue Date: | 12-Mar-2010 |
| Publisher: | Public Library of Science |
| Journal Title: | PLoS Pathogens |
| Volume: | 6 |
| Issue: | 3 |
| Start Page: | e1000801 |
| Publisher DOI: | 10.1371/journal.ppat.1000801 |
| Abstract: | Virus infections can result in a range of cellular injuries and commonly this involves both the plasma and intracellular membranes, resulting in enhanced permeability. Viroporins are a group of proteins that interact with plasma membranes modifying permeability and can promote the release of viral particles. While these proteins are not essential for virus replication, their activity certainly promotes virus growth. Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease resulting from lytic infection of oligodendrocytes by the polyomavirus JC virus (JCV). The genome of JCV encodes six major proteins including a small auxiliary protein known as agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to viral propagation at various stages in the replication cycle, including transcription, translation, processing of late viral proteins, assembly of virions, and viral propagation. Previous studies from our and other laboratories have indicated that JCV agnoprotein plays an important, although as yet incompletely understood role in the propagation of JCV. Here, we demonstrate that agnoprotein possesses properties commonly associated with viroporins. Our findings demonstrate that: (i) A deletion mutant of agnoprotein is defective in virion release and viral propagation; (ii) Agnoprotein localizes to the ER early in infection, but is also found at the plasma membrane late in infection; (iii) Agnoprotein is an integral membrane protein and forms homo-oligomers; (iv) Agnoprotein enhances permeability of cells to the translation inhibitor hygromycin B; (v) Agnoprotein induces the influx of extracellular Ca2+; (vi) The basic residues at amino acid positions 8 and 9 of agnoprotein key are determinants of the viroporin activity. The viroporin-like properties of agnoprotein result in increased membrane permeability and alterations in intracellular Ca2+ homeostasis leading to membrane dysfunction and enhancement of virus release. |
| Rights: | http://creativecommons.org/licenses/by/2.5/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/43091 |
| Appears in Collections: | 人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 澤 洋文
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