A protein kinase A-dependent mechanism by which rotavirus affects the distribution and mRNA level of the functional tight junction-associated protein, occludin, in human differentiated intestinal Caco-2 cells

J Virol. 2007 Aug;81(16):8579-86. doi: 10.1128/JVI.00263-07. Epub 2007 Jun 6.

Abstract

We found that at the tight junctions (TJs) of Caco-2 cell monolayers, rhesus monkey rotavirus (RRV) infection induced the disappearance of occludin. Confocal laser scanning microscopy showed the disappearance of occludin from the cell-cell boundaries without modifying the expression of the other TJ-associated proteins, ZO-1 and ZO-3. Western immunoblot analysis of RRV-infected cells showed a significant fall in the levels of the nonphosphorylated form of occludin in both Triton X-100-insoluble and Triton X-100-soluble fractions, without any change in the levels of the phosphorylated form of occludin. Quantitative reverse transcription-PCRs revealed that the level of transcription of the gene that encodes occludin was significantly reduced in RRV-infected cells. Treatment of RRV-infected cells with Rp-cyclic AMP and protein kinase A inhibitors H89 and KT5720 during the time course of the infection restored the distribution of occludin and a normal level of transcription of the gene that encodes occludin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caco-2 Cells
  • Carbazoles / pharmacology
  • Cell Fractionation
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Humans
  • Indoles / pharmacology
  • Intestines / cytology
  • Intestines / enzymology
  • Intestines / virology*
  • Isoquinolines / pharmacology
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microscopy, Confocal
  • Occludin
  • Octoxynol / chemistry
  • Phosphoproteins / analysis
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology
  • Pyrroles / pharmacology
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Rotavirus / physiology*
  • Sulfonamides / pharmacology
  • Thionucleotides / pharmacology
  • Tight Junctions / chemistry
  • Tight Junctions / enzymology
  • Tight Junctions / virology*
  • Transcription, Genetic
  • Zonula Occludens-1 Protein
  • Zonula Occludens-2 Protein

Substances

  • Carbazoles
  • Indoles
  • Isoquinolines
  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • Phosphoproteins
  • Protein Kinase Inhibitors
  • Pyrroles
  • RNA, Messenger
  • Sulfonamides
  • TJP1 protein, human
  • TJP2 protein, human
  • Thionucleotides
  • Zonula Occludens-1 Protein
  • Zonula Occludens-2 Protein
  • adenosine-3',5'-cyclic phosphorothioate
  • KT 5720
  • Octoxynol
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide