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

• Suzuki, Tadaki

• Orba, Yasuko

• Makino, Yoshinori

• Okada, Yuki

• Sunden, Yuji

• Hasegawa, Hideki

• Hall, William W.

• Sawa, Hirofumi

抄録

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.

収録刊行物

• Proceedings of the National Academy of Sciences of the United States of America

  Proceedings of the National Academy of Sciences of the United States of America 110 (46), 18668-18673, 2013-11-12

  The National Academy of Sciences

キーワード

• pathogen-host cell interaction
• intracellular vesicular trafficking

詳細情報

• CRID: 1050001339014585088
• NII論文ID: 120005429604
• HANDLE: 2115/55727
• ISSN: 00278424
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles