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.

Infection Studies in Pigs and Porcine Airway Epithelial Cells Reveal an Evolution of A(H1N1)pdm09 Influenza A Viruses Toward Lower Virulence

“…Tight junctions connecting the cells in the epithelial layer prevent the paracellular entry of foreign substances including pathogenic microorganisms [12,13]. Air-liquid interface (ALI) cultures of respiratory epithelial cells from different species-that is, humans, ferrets, pigs, mice, and cattle [14][15][16][17][18]-have been used to analyze infections by respiratory viruses. Recently it has been shown that late during infection, the epithelial cell layer gets thinner because of a substantial loss of ciliated cells due to apoptosis; nevertheless, it retains its barrier function [18].…”

Infection of differentiated airway epithelial cells from caprine lungs by viruses of the bovine respiratory disease complex

“…Furthermore, slices can be generated in large amounts and cells are viable for at least one week. Recently we have reported that different viruses of the BRDC have developed different strategies to infect differentiated bovine respiratory epithelial cells (Kirchhoff et al, 2014). Here, we analyzed these viruses for their ability to infect differentiated caprine airway cells and thus to cross the species barrier.…”

Comparison of mono- and co-infection by swine influenza A viruses and porcine respiratory coronavirus in porcine precision-cut lung slices

“…Precision cut lung slices (PCLS) are a useful tool to analyze viral infiltration ex vivo. Lung slices have been used in scientific studies from a variety of animals like rodents, caprine or bovine lung or even human lung (Abdull Razis et al, 2011;Banerjee et al, 2012;Braun and Tschernig, 2006;Goris et al, 2009;Kirchhoff et al, 2014a;Kirchhoff et al, 2014b). However, although porcine PCLS have been analyzed in the context of influenza A virus infection and co-infection with bacteria, the co-infection with coronaviruses remains to be investigated (Meng et al, 2013;Punyadarsaniya et al, 2011;Wu et al, 2016).…”