Coxsackievirus entry across epithelial tight junctions requires occludin and the small GTPases Rab34 and Rab5.

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  • Author(s): Coyne CB;Coyne CB; Shen L; Turner JR; Bergelson JM
  • Source:
    Cell host & microbe [Cell Host Microbe] 2007 Sep 13; Vol. 2 (3), pp. 181-92.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 101302316 Publication Model: Print Cited Medium: Internet ISSN: 1934-6069 (Electronic) Linking ISSN: 19313128 NLM ISO Abbreviation: Cell Host Microbe Subsets: MEDLINE
    • Publication Information:
      Original Publication: Cambridge, Mass. : Cell Press
    • Subject Terms:
      Virus Internalization*; Enterovirus B, Human/*physiology ; Epithelial Cells/*virology ; Membrane Proteins/*physiology ; Tight Junctions/*virology ; rab GTP-Binding Proteins/*physiology ; rab5 GTP-Binding Proteins/*physiology; Caveolins/physiology ; Cell Line ; Dynamins/physiology ; Endocytosis/physiology ; Humans ; Occludin ; ras GTPase-Activating Proteins/physiology
    • Abstract:
      The major group B coxsackievirus (CVB) receptor is a component of the epithelial tight junction (TJ), a protein complex that regulates the selective passage of ions and molecules across the epithelium. CVB enters polarized epithelial cells from the TJ, causing a transient disruption of TJ integrity. Here we show that CVB does not induce major reorganization of the TJ, but stimulates the specific internalization of occludin-a TJ integral membrane component-within macropinosomes. Although occludin does not interact directly with virus, depletion of occludin prevents CVB entry into the cytoplasm and inhibits infection. Both occludin internalization and CVB entry require caveolin but not dynamin; both are blocked by inhibitors of macropinocytosis and require the activity of Rab34, Ras, and Rab5, GTPases known to regulate macropinocytosis. Thus, CVB entry depends on occludin and occurs by a process that combines aspects of caveolar endocytosis with features characteristic of macropinocytosis.
    • Comments:
      Comment in: Cell Host Microbe. 2007 Sep 13;2(3):143-6. doi: 10.1016/j.chom.2007.08.004. (PMID: 18005729)
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    • Grant Information:
      R01 DK061931 United States DK NIDDK NIH HHS; R01 DK061931-06 United States DK NIDDK NIH HHS; R01AI5228 United States AI NIAID NIH HHS
    • Accession Number:
      0 (Caveolins)
      0 (Membrane Proteins)
      0 (OCLN protein, human)
      0 (Occludin)
      0 (ras GTPase-Activating Proteins)
      EC 3.6.1.- (RAB39A protein, human)
      EC 3.6.5.2 (rab GTP-Binding Proteins)
      EC 3.6.5.2 (rab5 GTP-Binding Proteins)
      EC 3.6.5.5 (Dynamins)
    • Publication Date:
      Date Created: 20071117 Date Completed: 20071211 Latest Revision: 20211020
    • Publication Date:
      20250114
    • Accession Number:
      PMC2719558
    • Accession Number:
      10.1016/j.chom.2007.07.003
    • Accession Number:
      18005733