Regulation of polymeric immunoglobulin receptor expression by reovirus.
Polymeric immunoglobulin receptor (pIgR) transcytoses dimeric IgA and IgA-coated immune complexes from the lamina propria across epithelia and into secretions. The effect of reovirus infection on regulation of pIgR expression in the human intestinal epithelial cell line HT-29 was characterized in this report. Both replication-competent and UV-inactivated reovirus at m.o.i. equivalents of 1-100 p.f.u. per cell upregulated pIgR mRNA by 24 h post-infection and intracellular pIgR protein was increased at 48 h following exposure to UV-inactivated virus. Binding of virus to HT-29 cells was required, as pre-incubating virus with specific antiserum, but not non-immune serum, inhibited reovirus-mediated pIgR upregulation. Endosomal acidification leading to uncoating of virus is a required step for pIgR upregulation, as ammonium chloride or bafilomycin A1 pre-treatment inhibited virus-induced pIgR upregulation. Inhibition experiments using the calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal suggested that calpains are involved in reovirus-mediated pIgR upregulation. Upregulation of pIgR following virus infection appears to be an innate immune response against invading pathogens that could help the host clear infection effectively. Signalling induced by microbes and their products may serve to augment pIgR-mediated transcytosis of IgA, linking the innate and acquired immune responses to viruses.
Pal
Kasturi
K
Department of Microbiology, Immunology and Cell Biology, Robert C. Byrd Health Sciences Center, West Virginia University, PO Box 9177, Morgantown, WV 26506-9177, USA.
Kaetzel
Charlotte S
CS
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA.
Brundage
Kathleen
K
Department of Microbiology, Immunology and Cell Biology, Robert C. Byrd Health Sciences Center, West Virginia University, PO Box 9177, Morgantown, WV 26506-9177, USA.
Cunningham
Cynthia A
CA
Department of Microbiology, Immunology and Cell Biology, Robert C. Byrd Health Sciences Center, West Virginia University, PO Box 9177, Morgantown, WV 26506-9177, USA.
Cuff
Christopher F
CF
Department of Microbiology, Immunology and Cell Biology, Robert C. Byrd Health Sciences Center, West Virginia University, PO Box 9177, Morgantown, WV 26506-9177, USA.
D002154:Calpain / Q000037:antagonists & inhibitors / Q000502:physiology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000821:virology; D007976:Leupeptins / Q000494:pharmacology; D012089:Mammalian orthoreovirus 3 / Q000276:immunology* / Q000528:radiation effects; D019056:Receptors, Polymeric Immunoglobulin / Q000378:metabolism*; D014466:Ultraviolet Rays; D015854:Up-Regulation
D007976:Leupeptins; D019056:Receptors, Polymeric Immunoglobulin; C063261:acetylleucyl-leucyl-norleucinal; D002154:Calpain