Epithelial cell polarization is a determinant in the infectious outcome of immunoglobulin a-mediated entry by Epstein-Barr virus
Epithelial cell polarization is a determinant in the infectious outcome of immunoglobulin a-mediated entry by Epstein-Barr virus
复制标题
DOI：
10.1128/jvi.71.1.519-526.1997
复制
发表时间：
1997-01-01
影响因子：
5.4
通讯作者：
Sixbey, JW
中科院分区：
文献类型：
--
作者：
Gan, YJ;Chodosh, J;Sixbey, JW
由于EB病毒(EBV)感染引起的鼻咽上皮疾病通常发生在预先存在病毒特异性抗体的慢性病毒携带者中，体外研究表明，EBV特异性免疫球蛋白A(IgA)可促进人类上皮细胞的感染，否则通过聚合免疫球蛋白受体(PIgR)对EBV具有抵抗力。为了确定EBV在体内是否类似地利用IgA的转运机制，我们检测了小鼠血液中IgA-EBV复合体的命运，其中pIgR介导的IgA免疫复合体通过肝细胞清除循环中的外源性抗原，通过聚合酶链式反应分析表明，在病毒感染的小鼠中，A-EBV的肝胆转运，但没有通过免疫染色检测到肝细胞感染。由于EBV免疫复合体的有效转运可能避免感染结局，我们在转导pIgR的极化的Madin-Darby犬肾(MDCK)细胞中调节了跨细胞途径以确定其对病毒抗原表达的影响，就像体内的肝细胞一样，极化单层中的MDCK细胞将IgA-EBV从基底细胞面转位到顶端介质中，但没有证据表明感染。然而，当以未极化的单细胞悬液暴露于IgA-EBV时，MDCK细胞立即-早期和早期表达EBV抗原。这些结果表明，pIgR介导的PigA-EBV通过上皮细胞传递促进了EBV在长期病毒携带者中的内源性传播。感染局限于与先前的细胞病理学不同的极性改变的细胞。
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.