Interactions between Paramyxoviruses and Bacteria: Implications for Pathogenesis and Intervention

Globally, respiratory tract diseases caused by bacteria and viruses are an important burden of disease. Respiratory bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus) can colonize the upper respiratory tract. The same area can be shared with respiratory viruses such as human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV). Therefore, it is possible that these bacteria and viruses can interact with each other, potentially resulting in a worse disease outcome. The research described in this thesis comprehend interactions between respiratory bacteria and viruses. Chapter 2 described the effect of several bacterial components on HRSV infections in cell cultures. One tested bacterial components (Pam3CSK4) can significantly enhance HRSV infections. The use of Pam3CSK4 as adjuvant for live-attenuated virus vaccine has been tested in two animal models. In chapter 3 a live-attenuated canine distemper virus (CDV) has been used. Animals were vaccinated intranasally. The infection-enhancing property of Pam3CSK4 in this animal model was confirmed. In chapter 4 a similar study was conducted with a live-attenuated candidate virus vaccine. Unfortunately, in this second animal model the addition of Pam3CSK4 did not had a beneficial effect. To translate laboratory studies to humans it is essential to use models which simulate reality as good as possible. Chapter 5 describes how a new genetic modified HRSV expressing a fluorescent protein was generated and characterised. This virus can be considered as a wild-type virus, but, upon infection this virus can be detected quickly and sensitively. In Chapter 6 a new ex vivo model system has been described. It is known that after viral respiratory infections bacterial infections can occur, so called secondary bacterial infections or bacterial superinfections. Chapter 7 described the interactions between different respiratory bacteria and HMPV. It can be concluded, that an interaction between pneumococcal carriage and HMPV infection exists. In Chapter 8 a potential interaction between carriage of different pneumococcus variants and HRSV has been studied. It was shown that pneumococcus serotype 19F could significantly enhance HRSV infection in vitro and in vivo. In conclusion the research described in this thesis has led to new insights in interactions between respiratory bacteria and viruses and to better insights in the pathogenesis of HRSV. Especially the new developed virus will further be used in other fields of HRSV research. Thereby magnifying our understanding of the virus. This will have great advantages for the development of a HRSV vaccine and new effective intervention strategies.