title: The role of immunoglobulin A in prolonged and relapsing hepatitis A virus infections.
abstract: Hepatitis A virus (HAV) infections result in different courses of the disease, varying between normal, prolonged and relapsing. However, the reason for these heterogeneous clinical appearances is not understood. As HAV-anti-HAV IgA immunocomplexes (HAV-IgA) infect hepatocytes, IgA was postulated as a carrier supporting hepatotropic transport of HAV, and it was speculated that this carrier mechanism contributes to the various clinical outcomes. In this study, the IgA-carrier mechanism was investigated in a mouse model. We show that HAV-IgA immunocomplexes efficiently reached the liver not only in HAV-seronegative mice, but also, and this is in contrast to free-HAV particles, in immunized HAV-seropositive animals. This IgA-mediated transport of HAV to the liver in the presence of immunity depended on the stage of development of the immune response. We conclude that over a period of several weeks after infection, anti-HAV IgA is able to promote an enterohepatic cycling of HAV, resulting in continuous endogenous reinfections of the liver. Our experiments indicate that highly avid IgG antibodies, which are present at later times of the infection, can terminate the reinfections. However, the endogenous reinfections in the presence of a developing neutralizing immunity might contribute to prolonged as well as to relapsing courses of HAV infections. Furthermore, the results show that serum IgA may act as an infection protracting factor.
authors.affiliation: Department of Virology, University of Bremen, Leobener Straße/UFT, D-28359 Bremen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Dotzauer
authors.affiliation: QIAGEN Hamburg GmbH, Königstr. 4a, D-22767 Hamburg, Germany.
authors.forename: Alke
authors.initials: A
authors.lastname: Heitmann
authors.affiliation: Altona Diagnostics GmbH, Mörkenstr. 12, D-22767 Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Laue
authors.affiliation: Department of Virology, University of Bremen, Leobener Straße/UFT, D-28359 Bremen, Germany.
authors.forename: Leena
authors.initials: L
authors.lastname: Kraemer
authors.affiliation: Department of Neurosurgery, Medical School Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schwabe
authors.affiliation: Department of Virology, University of Bremen, Leobener Straße/UFT, D-28359 Bremen, Germany.
authors.forename: Dajana
authors.initials: D
authors.lastname: Paulmann
authors.affiliation: Children's Hospital, Department 1, University of Tübingen, Silcherstraße 7, D-72076 Tübingen, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Flehmig
authors.affiliation: Department of Virology, University of Bremen, Leobener Straße/UFT, D-28359 Bremen, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Vallbracht
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D006506:Hepatitis A / Q000276:immunology* / Q000821:virology; D022362:Hepatitis A Vaccines / Q000276:immunology; D030041:Hepatitis A virus / Q000276:immunology* / Q000502:physiology; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology*; D008099:Liver / Q000821:virology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012008:Recurrence
chemical_list: D057134:Antibodies, Neutralizing; D022362:Hepatitis A Vaccines; D007070:Immunoglobulin A