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 (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.
Gan
Y J
YJ
Program in Viral Oncogenesis and Tumor Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Chodosh
J
J
Morgan
A
A
Sixbey
J W
JW
D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D004285:Dogs; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019056:Receptors, Polymeric Immunoglobulin / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000276:immunology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D007070:Immunoglobulin A; D019056:Receptors, Polymeric Immunoglobulin; D014763:Viral Matrix Proteins