title: Specific IgA Enhances the Transcytosis and Excretion of Hepatitis A Virus.
abstract: Hepatitis A virus (HAV) replicates in the liver, and is excreted from the body in feces. However, the mechanisms of HAV transport from hepatocytes to the gastrointestinal tract are poorly understood, mainly due to lack of suitable in vitro models. Here, we use a polarized hepatic cell line and in vivo models to demonstrate vectorial transport of HAV from hepatocytes into bile via the apical cell membrane. Although this transport is specific for HAV, the rate of fecal excretion in inefficient, accounting for less than 1% of input virus from the bloodstream per hour. However, we also found that the rate of HAV excretion was enhanced in the presence of HAV-specific IgA. Using mice lacking the polymeric IgA receptor (pIgR(-/-)), we show that a proportion of HAV:IgA complexes are transported via the pIgR demonstrating a role for specific antibody in pathogen excretion.
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Counihan
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Anderson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018938:Caco-2 Cells; D017927:Calicivirus, Feline / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D016764:Cell Polarity; D002478:Cells, Cultured; D005243:Feces / Q000821:virology; D030041:Hepatitis A virus / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D011961:Receptors, Fc / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology / Q000302:isolation & purification; D057900:Transcytosis
chemical_list: C045281:IgA receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc; D011994:Recombinant Proteins