title: Three viruses of the bovine respiratory disease complex apply different strategies to initiate infection.
abstract: Bovine respiratory disease complex (BRDC) is the major cause of serious respiratory tract infections in calves. The disease is multifactorial, with either stress or reduced immunity allowing several pathogens to emerge. We investigated the susceptibility of bovine airway epithelial cells (BAEC) to infection by the three major viruses associated with the BRDC: bovine respiratory syncytial virus (BRSV), bovine herpesvirus type 1 (BHV-1) and bovine parainfluenza virus type 3 (BPIV3). For this purpose, two culture systems for well-differentiated BAEC were used: the air-liquid interface (ALI) system, where filter-grown BAEC differentiate into a pseudostratified respiratory epithelium and precision-cut lung slices (PCLS) where BAEC are maintained in the original tissue organisation. Comparative infection studies demonstrated that entry and release of BPIV3 occurred specifically via the apical membrane with ciliated cells being the major target cells. By contrast, airway epithelial cells were largely resistant to infection by BHV-1. When the epithelial barrier was abolished by opening tight junctions or by injuring the cell monolayer, BHV-1 infected mainly basal cells. Respiratory epithelial cells were also refractory to infection by BRSV. However, this virus infected neither differentiated epithelial cells nor basal cells when the integrity of the epithelial barrier was destroyed. In contrast to cells of the airway epithelium, subepithelial cells were susceptible to infection by BRSV. Altogether, these results indicate that the three viruses of the same disease complex follow different strategies to interact with the airway epithelium. Possible entry mechanisms are discussed.
authors.forename: Jana
authors.initials: J
authors.lastname: Kirchhoff
authors.forename: Sabine
authors.initials: S
authors.lastname: Uhlenbruck
authors.forename: Katherina
authors.initials: K
authors.lastname: Goris
authors.forename: Günther M
authors.initials: GM
authors.lastname: Keil
authors.affiliation: Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany. Georg.Herrler@tiho-hannover.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Herrler
mesh_terms: D000818:Animals; D048090:Bovine Respiratory Disease Complex / Q000821:virology*; D001980:Bronchi / Q000821:virology*; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D007242:Herpesvirus 1, Bovine / Q000502:physiology; D007241:Infectious Bovine Rhinotracheitis / Q000821:virology*; D008856:Microscopy, Fluorescence / Q000662:veterinary; D029101:Parainfluenza Virus 3, Bovine / Q000502:physiology; D020545:Respiratory Mucosa / Q000166:cytology / Q000821:virology*; D018357:Respiratory Syncytial Virus Infections / Q000662:veterinary* / Q000821:virology; D018112:Respiratory Syncytial Virus, Bovine / Q000502:physiology; D010253:Respirovirus Infections / Q000662:veterinary* / Q000821:virology; D014709:Vero Cells