Diseases of the nasopharyngeal epithelium due to Epstein-Barr virus (
EBV) infection typically occur in chronic virus carriers with preexisting virus-specific
antibodies. In vitro studies have shown that EBV-specific
immunoglobulin A (
IgA) promotes
infection of human epithelial cells, otherwise refractory to EBV, via the
polymeric immunoglobulin receptor (pIgR). To determine if EBV similarly exploits
IgA transport mechanisms in vivo, we examined the fate of
IgA-EBV complexes in the blood of mice, where pIgR-mediated transcytosis of
IgA immune complexes through hepatocytes eliminates exogenous
antigens from the circulation. By PCR analysis we showed hepatobiliary transport of
IgA-EBV in viremic mice, but without detectable hepatocellular
infection by immunostaining. Because efficient transport of EBV
immune complexes might avert an infectious outcome, we modulated the transcytotic pathway in polarized Madin-Darby canine kidney (MDCK) cells transfected with pIgR to determine the effect on
viral antigen expression. Like hepatocytes in vivo, MDCK cells in polarized monolayers translocated
IgA-EBV from the basal cell face into apical medium without evidence for
infection. However, when exposed to
IgA-EBV as unpolarized single-cell
suspensions, MDCK cells expressed EBV immediate-early and early
antigens. These results suggest that pIgR-mediated transcytosis of pIgA-EBV through epithelium facilitates endogenous spread of EBV in long-term virus carriers, with
infection being confined to cells with altered polarity from prior cytopathology.