Transmissible gastroenteritis virus (TGEV) is a porcine coronavirus that causes intestinal infections. Among piglets, mortality may reach up to 100%. An important pathogenicity factor is the viral surface protein S with its sialic acid binding activity. The affinity for sialic acid enables the S protein to attach to a mucin-type glycoprotein (MGP) present in brushborder membranes of the intestinal epithelium. Aim of this project is to isolate this host protein and to determine the amino acid sequence. Based on the sequence data we will develop probes for histological analyses to determine the distribution of the glycoprotein in intestinal tissues. Age-dependent differences in the expression of MGP will also be analyzed. This work will contribute to our understanding of the role of the mucin-type glycoprotein for the enteropathogenicity of TGEV.

An important result of our recent research was the finding that the S protein of TGEV – in contrast to the homologous protein of the SARS-associated coronavirus – is retained within the endoplasmic reticulum and not transported to the cell surface. In our future work we will characterize the retention signal in the cytoplasmic tail of the S protein in more detail. TGEV mutants with modifications of the retention motif will be generated and analyzed for their replication kinetics in cell culture. By infecting pigs, the effect of the mutations on the pathogenicity will be determined. These studies will help to understand the enterotropism and the enteropathogenicity of TGEV. This knowledge will allow to develop models for intestinal infections that are applicable also to other enteropathogenic viruses and thus may be the basis for new antiviral strategies.