The 3-dimensional play of human parechovirus infection; Cell, virus and antibody

HPeV3 has been shown to be the ‘odd one out’ compared to the other genotypes; HPeV3 is more often associated with severe disease, infects significantly younger infants, seems to be more difficult to culture, and does not recombine with other HPeV types. The aim of this thesis is to study whether these differences could be explained by differences in viral tropism and Ab protection between the subsequent HPeV types. The first part of the thesis focuses on differences in viral tropism among HPeV types. In Chapter 2, we describe the growth characteristics of the different genotypes on different cell lines. To more extensively look into the differences between HPeV3 an HPeV1 related to the clinical outcome of infection, we describe the specific cell tropism and neutralization of human parechovirus types 1 and 3 in Chapter 3. To study the importance of the human airway as a primary replication site of HPeVs and differences in virus tropism, we determined replication kinetics of different HPeVs types in a human respiratory primary cell culture system (HAE) (Chapter 4). The second part of the manuscript focuses on neutralization of HPeVs. Chapter 5 describes the seroprevalence of neutralizing (protective) Abs among different groups in Finland and the Netherlands. The (cross-) neutralization of HPeVs by different HPeV1 and HPeV3 polyclonal and monoclonal Abs is extensively described in Chapter 6 and 8. Using cryo-EM, we determined the different neutralizing epitopes for HPeV1 (Chapter 7) and we revealed a high-resolution structure of HPeV3 (Chapter 9).