In humans, viral infections causing respiratory disease have been known for many years. Every now and then such viruses may cause epidemics involving large groups of people or even pandemics with spread across the world. At the end of last century and at the beginning of this century zoonotic viruses emerged that were of serious risk for the human population: severe acute respiratory syndrome (SARS) caused by SARS coronavirus (CoV), highly pathogenic avian influenza (HPAI) virus H5N1, and pandemic influenza virus A(H1N1)pdm09 (pH1N1). Both SARS-CoV and influenza A viruses cause respiratory disease that may lead to severe and even fatal cases of pneumonia. The course and outcome of the infections is related to their pathogenesis, which can be explored by describing and comparing pathology, virology, and genomics. Understanding the pathogenesis of SARS and influenza is valuable for development of therapeutic and preventive strategies. Since the pathology of acute human fatal cases in SARS and influenza is rarely described, there is a need for animal models to provide information about the early stage of the disease. Also, pathological description of human cases with uncomplicated viral pneumonia is sparse because patients have multiple therapeutic interventions and secondary co-infections that may alter the pathology. Interestingly, the pathology of SARS-CoV and influenza virus infections has similar features; however, there are also differences in disease outcome. This thesis focusses on the pathology of SARS-CoV and influenza A virus infections in experimental animals. The pathology of these virus infections in animals is compared to that in humans and is related to the pathogenesis. The animal species that are used in this thesis to study the pathology of SARS-CoV infection are; cynomolgus macaques, African Green monkeys, ferrets, and cats. The pathology of influenza virus infection was studied in cynomolgus macaques, ferrets, and cats. Additionally, temporal and spatial dynamics for the pathology of different influenza virus infections in ferrets is described in a time course experiment. Finally, the effect of vaccination on the pathology is studied in ferrets and cynomolgus macaques for SARS-CoV infection and in ferrets for pH1N1 infection.

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Keywords SARS, epidemiology, infectious diseases, influenza, virology
Promotor T. Kuiken (Thijs) , A.D.M.E. Osterhaus (Albert)
Publisher Erasmus University Rotterdam
Sponsor The research described in this thesis was conducted at the Department of Viroscience, Erasmus MC, Rotterdam, at Viroclinics Biosciences BV, Rotterdam, and at NVI, de Bilt, The Netherlands with financial support of the Virgo consortium, an Innovative Cluster installed by the Netherlands Genomics Initiative and of the Dutch Government (grant BSIK 03012), NIH (grant HL080621- 01A1), DISSECT (European grant SP22-CT-2004-511060), NIAID-NIH (contract HHSN266200700010C), EU FP6 FLUVAC (044407), EU FP7 EMPERIE (project 223498), FP7 ADITEC (project 280873), TI Pharma (grant T4-214). Further financial support for printing of this thesis by the following companies and foundations is gratefully acknowledged: Novartis Vaccines and Diagnostics Star-Oddi ( Viroclinics Biosciences BV J.E. Jurriaanse Stichting Dako Benelux
ISBN 978-94-90320-00-3
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Grant This work was funded by the European Commission 7th Framework Programme; grant id fp7/223498 - European management platform for emerging and re-emerging infectious disease entities (EMPERIE), This work was funded by the European Commission 6th Framework Programme; grant id fp6/044407 - Increased immunogenicity of pandemic influenza vaccine (FLUVAC), This work was funded by the European Commission 6th Framework Programme; grant id fp6/511060 - Development of intervention strategies against SARS in a European -Chinese taskforce (DISSECT), This work was funded by the European Commission 7th Framework Programme; grant id fp7/280873 - Advanced Immunization Technologies (ADITEC)
van den Brand, J.M.A. (2013, January 17). Experimental SARS and influenza: similar disease, different pathways. Erasmus University Rotterdam. Retrieved from