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Viroporin activity of the JC polyomavirus is regulated by interactions with the adaptor protein complex 3

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Title: Viroporin activity of the JC polyomavirus is regulated by interactions with the adaptor protein complex 3
Authors: Suzuki, Tadaki Browse this author
Orba, Yasuko Browse this author
Makino, Yoshinori Browse this author
Okada, Yuki Browse this author
Sunden, Yuji Browse this author
Hasegawa, Hideki Browse this author
Hall, William W. Browse this author
Sawa, Hirofumi Browse this author →KAKEN DB
Keywords: pathogen-host cell interaction
intracellular vesicular trafficking
Issue Date: 12-Nov-2013
Publisher: The National Academy of Sciences
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 110
Issue: 46
Start Page: 18668
End Page: 18673
Publisher DOI: 10.1073/pnas.1311457110
Abstract: Viroporins, which are encoded by a wide range of animal viruses, oligomerize in host cell membranes and form hydrophilic pores that can disrupt a number of physiological properties of the cell. Little is known about the relationship between host cell proteins and viroporin activity. The human JC polyomavirus (JCV) is the causative agent of progressive multifocal leukoencephalopathy. The JCV-encoded agnoprotein, which is essential for viral replication, has been shown to act as a viroporin. Here we demonstrate that the JCV agnoprotein specifically interacts with adaptor protein complex 3 through its delta subunit. This interaction interrupts adaptor protein complex 3-mediated vesicular trafficking with suppression of the targeting of the protein to the lysosomal degradation pathway and instead permits the transport of agnoprotein to the cell surface with resulting membrane permeabilization. The findings demonstrate a previously undescribed paradigm in virus-host interactions allowing the host to regulate viroporin activity and suggest that the viroporins of other viruses may also be highly regulated by specific interactions with host cell proteins.
Type: article (author version)
URI: http://hdl.handle.net/2115/55727
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)

Submitter: 澤 洋文

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