Infection of polarized bovine respiratory epithelial cells by bovine viral diarrhea virus (BVDV)

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 the 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 the 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, the 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.

Canid herpesvirus 1 Preferentially Infects Polarized Madin-Darby Canine Kidney Cells from the Basolateral Surface

“…It has been shown that asymmetric distribution of nectin-1, one of the HSV-1 receptors, contributes to the preferential infection of the apical surface of polarized epithelial cells by this virus [13]. Furthermore, because we found that CHV-1 can infect both the apical and basolateral surfaces of MDCK cells, we cannot rule out the possibility that different receptors mediate entry at each of the two surfaces, which appears to be the case for infection of bovine airway epithelial cells by bovine diarrhea virus [15]. Identification of the cellular receptor(s) for CHV-1 will be an important step towards answering this question.…”

“…For example, HSV-1 infects polarized human uterine (ECC-1), colonic (CaCo-2), and retinal pigment (ARPE-19) epithelial cells more efficiently from the apical surface [13]. Moreover, it has been reported that the asymmetric distribution of cellular receptors on polarized cells for certain viruses promotes the preferential entry of the virus from the apical or basolateral surface including Ebola virus [14] and bovine viral diarrhea virus [15]. We next tested whether CHV-1 infected the apical or basolateral surface of polarized MDCK cells more efficiently or whether there was no difference.…”

A β-Hairpin Motif in the Envelope Protein E2 Mediates Receptor Binding of Bovine Viral Diarrhea Virus

“…It is well established that treatment of MDBK cells with monoclonal antibodies against CD46 can block infection [ 10 , 11 ]. Interestingly, polarized bovine respiratory epithelial cells only express CD46 on the apical side, and accordingly, treatment with monoclonal antibodies against CD46 blocked BVDV infection from the apical surface [ 31 ]. However, respiratory epithelial cells were efficiently infected by BVDV from the basolateral side despite the absence of CD46 at the basolateral surface, suggesting a CD46 independent entry mechanism.…”

Non-structural proteins of bovine viral diarrhea virus

“…BVDV-1 and BVDV-2 can infect domestic and wild animals, including cattle, sheep, goats, deer, and camel. Among these susceptible animals, the clinical signs in BVDV-infected cattle are the most serious, including diarrhea, respiratory disease, immunosuppression, growth retardation, abortion, and decreased reproductive efficiency, which poses a serious impact on the production and health of the cattle herd [ 6 ]. Therefore, the World Organization for Animal Health (OIE) lists BVD as a Class B infectious disease, and BVDV control and eradication plans are in place in most of Europe, the USA, and the UK [ 7 ].…”