Abstract

Bovine viral diarrhea virus (BVDV) is affecting cattle populations all over the world causing acute disease, immunosuppressive effects, respiratory diseases, gastrointestinal and reproductive failure in cattle. The virus is taken up via the oronasal route and infection of epithelial and immune cells contributes to dissemination of the virus throughout the body. However, it is not known how the virus gets across the barrier of epithelial cells encountered in the airways. Here, we analyzed the infection of polarized primary bovine airway epithelial cells (BAEC). Infection of BAEC by a non-cytopathogenic BVDV was possible via both the apical and the basolateral plasma membrane, but infection was most efficient, when the virus was applied to the basolateral plasma membrane. Irrespective of the site of infection, BVDV was efficiently released to the apical site, while only minor amounts of virus were detected in the basal medium. This indicates that the respiratory epithelium can release large amounts of BVDV to the environment and susceptible animals via respiratory fluids and aerosols, but BVDV cannot cross the airway epithelial cells to infect subepithelial cells and establish systemic infection. Further experiments showed that the receptor, bovine CD46, for BVDV is expressed predominantly on the apical membrane domain of the polarized epithelial cells. In a CD46 blocking experiment, addition of an antibody directed against CD46 almost completely inhibited apical infection, whereas basolateral infection was not affected. While CD46 serves as a receptor for apical infection of BAEC by BVDV, the receptor for basolateral infection remains to be elucidated.

摘要

牛病毒性腹泻病毒（BVDV）正在影响全世界的牛群，引起牛的急性疾病，免疫抑制作用，呼吸系统疾病，胃肠道和生殖衰竭。该病毒通过口鼻途径吸收，上皮和免疫细胞的感染有助于病毒在全身的传播。但是，尚不知道病毒如何穿越气道中遇到的上皮细胞屏障。在这里，我们分析了极化的原代牛气道上皮细胞（BAEC）的感染。非致病性BVDV可能通过顶端和基底外侧质膜感染BAEC，但是当将病毒应用于基底外侧质膜时，感染是最有效的。不论感染部位如何 BVDV被有效释放到根尖，而在基础培养基中仅检测到少量病毒。这表明呼吸道上皮可以通过呼吸液和气溶胶释放大量BVDV到环境和易感动物中，但是BVDV不能穿过气道上皮细胞感染上皮下细胞并建立全身感染。进一步的实验表明，BVDV的牛CD46受体主要在极化上皮细胞的顶膜结构域表达。在CD46阻断实验中，添加针对CD46的抗体几乎可以完全抑制根尖感染，而基底外侧感染则不受影响。尽管CD46充当BVDV对BAEC根尖感染的受体，但基底外侧感染的受体仍有待阐明。