EPITHELIAL-CELL POLARIZATION IS A DETERMINANT IN THE INFECTIOUS OUTCOME OF IMMUNOGLOBULIN A-MEDIATED ENTRY BY EPSTEIN-BARR-VIRUS

Diseases of the nasopharyngeal epithelium due to Epstein-Barr virus (E BV) infection typically occur in chronic virus carriers with preexisti ng virus-specific antibodies, In vitro studies have shown that EBV-spe cific immunoglobulin A (IgA) promotes infection of human epithelial ce lls, otherwise refractory to EBV, via the polymeric immunoglobulin rec eptor (pIgR), To determine if EBV similarly exploits IgA transport mec hanisms in vivo, we examined the fate of IgA-EBV complexes in the bloo d of mice, where pIgR-mediated transcytosis of IgA immune complexes th rough hepatocytes eliminates exogenous antigens from the circulation, By PCR analysis we showed hepatobiliary transport of IgA-EBV in viremi c mice, but without detectable hepatocellular infection by immunostain ing. Because efficient transport of EBV immune complexes might avert a n infectious outcome, we modulated the transcytotic pathway in polariz ed Madin-Darby canine kidney (MDCK) cells transfected with pIgR to det ermine the effect on viral antigen expression, Like hepatocytes in viv o, MDCK cells in polarized monolayers translocated IgA-EBV from the ba sal cell face into apical medium without evidence for infection, Howev er, when exposed to IgA-EBV as unpolarized single-cell suspensions, MD CK cells expressed EBV immediate-early and early antigens, These resul ts suggest that pIgR-mediated transcytosis of pIgA-EBV through epithel ium facilitates endogenous spread of EBV in long-term virus carriers, with infection being confined to cells with altered polarity from prio r cytopathology.