Viral-bacterial co-infections:Effect of Streptococcus suis on influenza virus infections in differentiated porcine airway epithelial cells

• Applicant: Professor Dr. Georg Herrler
• Subject Area: Veterinary Medical Science
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 270348298

Co-infections in the respiratory tract play an important role in modern intensive production systems of agricultural animals, especially in pigs. Control of co-infections is a challenging task, since pathogenesis is much more complex as compared to mono-infections. Though this has been known for many years, little is known about the molecular mechanisms of interactions between pathogens and the host in co-Infections. It is very difficult to study this in animal infections and, therefore, it is important to develop suitable in vitro models which mimic the in vivo situation as closely as possible. In the proposed project, we will analyze the co-infection of airway epithelial cells by two important pathogens of the porcine respiratory tract: swine influenza viruses (SIV) and Streptococcus suis (S suis). Both agents are important also because of their ability to induce zoonotic infections. Aim of the project is to elucidate the interactions between influenza viruses and streptococci during co-infections of porcine airway epithelial cells. This a very focussed project, and thus, we will analyze only how the bacterial pathogen affects the virus infection. As the capsular polysaccharide of S. suis contains alpha2,6-linked sialic acid, SIV can bind to S. suis via the sialic acid-binding activity of the viral surface protein, haemagglutinin. We will determine the variations in these interactions by comparing different strains and variants of the two agents. Furthermore, it will be analyzed under which conditions and to what extent, the SIV-infection is affected by the SIV-S. suis interaction. This will be investigated not only with immortalized porcine tracheal cells but also with the actual target cells of the two pathogens, i.e. with differentiated airway epithelial cells. The latter will be cultivated as precision-cut lung slices or as air-liquid-interface cultures. In this way, the cells are accessible for reagents to elucidate molecular mechanisms such as the importance of sialic acid by pretreatment with neuraminidase. Apart from the capsular sialic acid, it will also be analyzed whether proteases of S. suis affect the course of the influenza virus infection by enhancing the proteolytic activation of the haemagglutinin which is a prerequisite of the viral fusion activity. The expected results will increase our understanding how S. suis affects in a co-infection scenario the SIV infection in the porcine respiratory tract. Based on this knowledge it will be possible to investigate in a follow-up project the indirect effects of one pathogen on the other, e.g. by inducing cytokine reactions in epithelial cells or immune cells like macrophages.

• DFG Programme: Research Grants