Pal Kasturi, Kaetzel Charlotte S, Brundage Kathleen, Cunningham Cynthia A, Cuff Christopher F
Department of Microbiology, Immunology and Cell Biology, Robert C. Byrd Health Sciences Center, West Virginia University, PO Box 9177, Morgantown, WV 26506-9177, USA.
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA.
J Gen Virol. 2005 Aug;86(Pt 8):2347-2357. doi: 10.1099/vir.0.80690-0.
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.
聚合免疫球蛋白受体（pIgR）将二聚体IgA和IgA包被的免疫复合物从固有层跨上皮转运至分泌物中。本报告描述了呼肠孤病毒感染对人肠上皮细胞系HT - 29中pIgR表达调控的影响。具有复制能力的呼肠孤病毒和紫外线灭活的呼肠孤病毒，在感染复数相当于每细胞1 - 100个空斑形成单位时，感染后24小时上调pIgR mRNA，暴露于紫外线灭活病毒后48小时细胞内pIgR蛋白增加。病毒与HT - 29细胞的结合是必需的，因为用特异性抗血清而非非免疫血清预孵育病毒可抑制呼肠孤病毒介导的pIgR上调。内体酸化导致病毒脱壳是pIgR上调的必要步骤，因为氯化铵或巴弗洛霉素A1预处理可抑制病毒诱导的pIgR上调。使用钙蛋白酶抑制剂N - 乙酰 - 亮氨酰 - 亮氨酰 - 正亮氨酸的抑制实验表明，钙蛋白酶参与呼肠孤病毒介导的pIgR上调。病毒感染后pIgR的上调似乎是针对入侵病原体的一种固有免疫反应，可帮助宿主有效清除感染。微生物及其产物诱导的信号传导可能有助于增强pIgR介导的IgA转胞吞作用，将针对病毒的固有免疫反应和获得性免疫反应联系起来。
