Globally, respiratory tract diseases caused by bacteria and viruses are an important burden of disease. Respiratory bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphyl

Nguyen, D.T. (Tien)

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

Erasmus University Digital Repository

Stellingen behorende bij het proefschriftInteractions between Paramyxoviruses and Bacteria:Implications for Pathogenesis and Intervention1.2.3.4.5.6.7.8.9.10.11.Positief geladen synthetische bacteriële lipopeptides kunnen de binding van membraanvirussen aan hun doelwitcel versterken (dit proefschrift). Het gebruik van infectie-versterkende synthetische bacteriële lipopeptides als hulpstof bij levend-verzwakte virus-vaccins lijkt geen grote toekomst te zijn beschoren (dit proefschrift). Genetisch gemodificeerde paramyxovirussen die fluorescente eiwitten tot expressie brengen leveren niet alleen artistieke foto’s, maar ook nieuwe inzichten in de ontwikkeling van ziekte op (dit proefschrift). Onderzoek naar de pathogenese van paramyxovirussen behoeft relevante virussen in de juiste modelsystemen (dit proefschrift). Het belang van virale versus bacteriële superinfecties wordt onderschat (dit proefschrift). Het tijdelijk immunologische geheugenverlies geïnduceerd door mazelen geeft bacteriën alle ruimte (de Vries et al., PLoS Pathog, 2012). Een halve eeuw HRSV vaccin onderzoek heeft nog geen mensenleven gered. Maternale vaccinatie biedt voor bescherming tegen HRSV grote mogelijkheden. Oncolytische virussen kunnen een belangrijke bijdrage leveren in de bestrijding van kanker. Het voorspellen van een grieppandemie zal een illusie blijven. Op het Erasmus MC gaan bacteriologen en virologen, net als 010 en 020, “hand in hand”.Duy Tien Nguyen26 juni 2014, Rotterdam

Interactions between Paramyxoviruses and Bacteria: Implications for Pathogenesis and Intervention

Abstract

Similar works

Full text

Available Versions

Erasmus University Digital Repository